Artificial synapses

ABSTRACT

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims benefit under 35 U.S.C. § 119(e) of U.S.Provisional Application No. US 62/970,374 filed Feb. 5, 2020, thecontents of which are incorporated herein by reference in theirentirety.

FIELD OF THE INVENTION

This invention relates to the generation of artificial synapses orextracellular vesicles, including features of extracellular vesiclesengineered to deliver signaling, for therapeutic use, includingtreatment of immune diseases and cancer.

BACKGROUND

Extracellular vesicles (EVs) play a critical role in intercellularcommunication by transferring microRNAs, lipids, and proteins toneighboring cells. The delivery of encapsulated molecules within EVs isa highly promising strategy as a therapeutic platform in many contexts,exploiting the unique biophysical and biochemical characteristics ofextracellular vesicles (EVs). However, there remains a great need in theart for a flexible and dynamic platform, where specific biologicalsignals can be reliably targeted without off-target effects and thatprovide a robust cellular response to achieve a therapeutic effect, suchas modulating inflammation.

SUMMARY

The compositions and methods provided herein are based, in part, on thediscovery that extracellular vesicles can be used to express engineeredfusion polypeptides that can modulate biological signal generation.These engineered vesicles, also termed artificial synapses, adopt thehallmark biophysical and biochemical features of extracellular vesicles,but are further engineered with vesicle targeting domains (e.g., stickybinders) and signaling domains, optionally joined by a linker withspecific functions. The fusion polypeptides provided herein are designedand produced as nucleic acid constructs (e.g., vectors) and expressed incells, such as mammalian cells. In particular, the vesicle targetingdomain of each fusion polypeptide anchors the polypeptide to theextracellular vesicle lipid membrane, thereby presenting the signalingdomain(s) of the polypeptide. The signaling domains on or within thevesicle membrane can make contact with recipient cells via targetpolypeptides (e.g., receptors on the extracellular surface of therecipient cell). Importantly, this strategy can allow for kineticallyfavorable signal generation and signal propagation. This includes, forexample, increasing density of agonist presentation to support receptorclustering of a target receptor located on a target cell—an onerousbarrier for traditional receptor targeting strategies.

This strategy was applied to alter immune checkpoint signaling, byengineering artificial synapses through genetic constructs with lipidbinding glycosylphosphatidylinositol (GPI) sticky binders joined withprogrammed death-ligand 1 (PD-L1) signaling domain, e.g., humanprogrammed death-ligand 1 (hPD-L1), expressed in cells and capable ofattachment to exosomes. Isolation, purification, and analysis ofartificial synapses revealed a high density of signaling domains of thehPD-L1-GPI fusion polypeptide. The hPD-L1 artificial synapse exosomesfurther demonstrated enhanced agonist signaling than soluble PD-L1ligand alone, supporting receptor clustering on a target cell. Whenapplied to a model of experimental autoimmune uveoretinitis (EAU), astatistically significant reduction in EAU symptoms was observed.

Thus, in one aspect, provided herein is an engineered extracellularvesicle or artificial vesicle comprising: at least one fusionpolypeptide comprising: at least one protein of interest (POI) domain;and at least one vesicle targeting domain. In some embodiments of any ofthe aspects, the engineered extracellular vesicle is an exosome. In someembodiments, of any of the aspects, the fusion protein further comprisesat least one linker. In some embodiments of any of the aspects, the POIdomain can substantially bind to a target polypeptide.

In another aspect, provided herein is an engineered extracellularvesicle comprising: at least one fusion polypeptide comprising:

-   -   (i) at least one protein of interest (POI) domain or a fragment        thereof; and    -   (ii) at least one vesicle targeting domain,    -   wherein the POI domain is in an extracellular position relative        to a lipid membrane of the extracellular vesicle.

In another aspect, provided herein is an engineered extracellularvesicle comprising:

-   -   (a) a first fusion polypeptide comprising:        -   (i) at least one protein of interest (POI) domain or a            fragment thereof; and        -   (ii) at least one vesicle targeting domain,    -   wherein the at least one POI domain is in an extracellular        position relative to a lipid membrane of the extracellular        vesicle,    -   (b) a second fusion polypeptide comprising:        -   (i) at least one protein of interest (POI) domain or a            fragment thereof; and        -   (ii) at least one vesicle targeting domain,            wherein the POI domain is in an extracellular position            relative to a lipid membrane of the extracellular vesicle,            and wherein the at least one vesicle targeting domain is            within a lipid membrane of the extracellular vesicle.

In another aspect, provided herein is an extracellular vesiclecomposition comprising: a plurality of artificial synapses,

wherein each artificial synapse comprises (i) an extracellular vesicle;(ii) one or more sticky binders; and (iii) one or more signalingdomains.

In another aspect, provided herein is a composition comprising aplurality of the engineered extracellular vesicles provided herein.

In another aspect, provided herein is a composition comprising two ormore of the engineered extracellular vesicles provided herein.

In another aspect, provided herein is a composition comprising three ormore of the engineered extracellular vesicles provided herein.

In another aspect, provided herein is a method of producing theengineered extracellular vesicle or the compositions provided herein,comprising:

-   -   (a) providing a population of cells expressing a vector        construct encoding one or more sticky binder and one or more        signaling domains; and    -   (b) isolating a plurality of artificial synapses from the        population of cells.

In another aspect, provided herein is a method of producing theengineered extracellular vesicle or the compositions provided herein,comprising:

-   -   (a) providing a population of cells expressing a vector        construct encoding one or more sticky binder and one or more        signaling domains; and    -   (b) isolating a plurality of artificial synapses from the        population of cells; and    -   (c) purifying the plurality of artificial synapses from the        population of cells.

In another aspect, provided herein is a method of modulatinginflammation in a subject, the method comprising:

-   -   administering a composition comprising a plurality of engineered        extracellular vesicles to a subject in need thereof,    -   wherein the engineered extracellular vesicles comprise at least        one fusion polypeptide comprising:        -   (i) at least one protein of interest (POI) domain or a            fragment thereof; and        -   (ii) at least one vesicle targeting domain.

In another aspect, provided herein is a use of a composition orengineered extracellular vesicle provided herein for the treatment of aninflammatory disease or condition.

In another aspect, provided herein is a use of a composition orengineered extracellular vesicle provided herein for the treatment of anautoimmune disease or condition.

In another aspect, provided herein is a use of a composition orengineered extracellular vesicle provided herein for the treatment ofcancer.

In one embodiment of any of the aspects, the engineered extracellularvesicle is an exosome.

In another embodiment of any of the aspects, the protein of interest(POI) domain or a fragment thereof is a N-terminal domain of the fusionpolypeptide. In another embodiment of any of the aspects, the POI domainis selected from the group consisting of: Table 1. In another embodimentof any of the aspects, the POI domain is PD-L1 or a fragment thereof. Inanother embodiment of any of the aspects, the POI domain is PD-L2 or afragment thereof. In another embodiment of any of the aspects, the POIdomain is FGL1 or a fragment thereof. In another embodiment of any ofthe aspects, the POI domain is 4-1BBL or a fragment thereof. In anotherembodiment of any of the aspects, the POI domain is CTLA-4 or a fragmentthereof. In another embodiment of any of the aspects, the protein ofinterest (POI) domain is HVEM or a fragment thereof.

In another embodiment of any of the aspects, the vesicle targetingdomain is a C-terminal domain of the fusion polypeptide. In anotherembodiment of any of the aspects, the vesicle targeting domain is in aluminal position relative to the lipid membrane of the extracellularvesicle. In another embodiment of any of the aspects, the vesicletargeting domain in an exterior position relative to the lipid membraneof the extracellular vesicle. In another embodiment of any of theaspects, the vesicle targeting domain is selected from the groupconsisting of: Table 3. In another embodiment of any of the aspects, thevesicle targeting domain is selected from the group consisting of: aGlycosylphosphatidylinositol (GPI) anchor, a fatty acetylation site, anda prenylation site. In another embodiment of any of the aspects, thevesicle targeting domain is C1C2. In another embodiment of any of theaspects, the vesicle targeting domain is a GPI anchor.

In another embodiment of any of the aspects, the fusion polypeptidecomprises at least two POI domains and/or at least two exosome targetingdomains.

In another embodiment of any of the aspects, the POI domainsubstantially binds to one or more of a target polypeptide. In anotherembodiment of any of the aspects, the target polypeptide is selectedfrom the group consisting of: Table 2.

In another embodiment of any of the aspects, the fusion polypeptidefurther comprises a peptide linker. In another embodiment of any of theaspects, the fusion polypeptide further comprises a fragmentcrystallizable region (Fc) domain. In another embodiment of any of theaspects, the linker is in an exterior position relative to the lipidmembrane of the extracellular vesicle. In another embodiment of any ofthe aspects, the linker is a transmembrane linker. In another embodimentof any of the aspects, the linker is in a luminal position relative tothe lipid membrane of the extracellular vesicle.

In another embodiment of any of the aspects, the engineeredextracellular vesicle does not comprise an endogenous POI polypeptide.

In another embodiment of any of the aspects, the composition furthercomprises a pharmaceutically acceptable carrier.

In another embodiment of any of the aspects, the one or more stickybinders or the vesicle targeting domain is selected from the groupconsisting of: a GPI anchor, a fatty acetylation site, and a prenylationsite.

In another embodiment of any of the aspects, the signaling domain or theprotein of interest comprises one or more of: PD-L1, PD-L2, CTLA-4(CD152), 4-1BBL (CD137L), HVEM (CD270), FGL1, OX-2 (CD200), Galectin-9,PVR (CD155), Nectin-2 (CD112) isoform alpha, Nectin-2 (CD112) isoformbeta, Nectin-2 (CD112) isoform delta, IL-10, TSG-6, B7-H3 (CD276), B7-H4(VTCN1), B7-H5 (VISTA), B7-H7 (HHLA2), BTNL1, VSIG8, VSIG3 (IGSF11),VSIG4, TIM-3 (HAVCR2), TIM-4 (TIMD4), CEACAM1, BTN3A1, BTN3A2, BTN2A1,BTNL8, BTN2A2, BTN1A1, TIGIT, CD27L (CD70), CD30L (CD153), GITRL, CD40L(CD154), LIGHT (CD258), TL1, CD80, CD86, LFA-3 (CD58), SLAM (CD150),CD40, CD28, CD28H, CD2, LFA-3 (CD58), CD48, CD226, DR3, DcR3, FasL,TIM-1 (CD365), PD-1, or active fragment thereof.

In another embodiment of any of the aspects, the isolating is via sizeexclusion chromatography. In another embodiment of any of the aspects,the purifying is via multimodal chromatography. In another embodiment ofany of the aspects, the method further comprises performing an assay forPOI binding to a target polypeptide.

In another embodiment of any of the aspects, the vector constructfurther encodes a promoter. In another embodiment of any of the aspects,the promoter is a tissue-specific promoter or an inducible promotor.

In one embodiment of any of the aspects, the method further comprisesselecting a subject that has or is suspected of having an autoimmunedisease or an inflammatory disease or condition. In another embodimentof any of the aspects, the inflammatory disease and/or condition isacute. In another embodiment of any of the aspects, the inflammatoryrelated disease and/or condition is chronic.

In another embodiment of any of the aspects, administering thecomposition provided herein comprises injection, topical administration,or inhalation.

A BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows construct representation of fusion polypeptides forlabeling an exosome surface with Type I membrane proteins.

FIG. 2A shows nucleic acid and translated protein sequences offull-length Phosphatidylserine binding: Lactadherin (MFGE8) C1C2.Underlined nucleic acid sequence highlights the sequence translated tothe C1C2 protein. Bold and underlined text highlights the C1C2 domainused to anchor signaling domains of interest (i.e. PD-L1 extracellulardomain) onto the surface of the Inventors' artificial synapses. FIG. 2Bshows nucleic acid and translated protein sequences of full length CD55(DAF) Glycosylphosphatidylinositol (GPI) anchor. Bold and underlinedtext highlights the GPI anchor domain used to anchor signaling domainsof interest (i.e. PD-L1 extracellular domain) onto the surface of theInventors' artificial synapses engineered from exosomes.

FIG. 3 demonstrates the nucleic acid and translated protein sequence forthe Fc linker used in genetically engineered constructs is shown in boldand underlined.

FIG. 4A demonstrates nucleic acid and translated protein sequence ofhuman PD-L1 (CD274). Bold and underlined sequence highlights the PD-L1extracellular domain used in the Inventors' artificial synapsesengineered from exosomes. FIG. 4B demonstrates nucleic acid and proteinsequence of human PD-L2. Bold and underlined sequence highlights thePD-L2 extracellular domain used in the Inventors' artificial synapsesengineered from exosomes. FIG. 4C shows mRNA and protein sequence ofhuman CTLA-4 (CD152). Bold and underlined sequence highlights the CTLA-4extracellular domain used in the Inventors' artificial synapses.

FIG. 5A shows an exemplary embodiment of pcDNA5-FRT cloning vector witha gene sequence coding for a fusion polypeptide inserted into a multiplecloning site. FIG. 5B shows an exemplary embodiment of the Gateway®destination vector pEF5-FRT-V5-DEST with a gene sequence coding for afusion polypeptide inserted into a multiple cloning site. The vectorswere used for constitutive high-level expression of fusion polypeptidedescribed herein in mammalian cells. FIG. 5C shows the nucleic acid andprotein sequence for the hCTLA4-Fc-GPI fusion polypeptide wherein thetext for the signaling domain is bolded, Fc linker is underlined, andsticky binder is italicized. FIG. 5D shows the nucleic acid and proteinsequence for the hPDL1-GPI-P2A-hHVEM-GPI fusion polypeptide wherein thetext for the signaling domain hPDL1 and hHVEM are bolded, P2A sequenceis underlined, and sticky binder GPI is italicized. With P2A included, aself-cleaving peptide sequence, artificial synapses with this featurewill have both hPDL1-GPI and hHVEM-GPI loaded onto the surface. FIG. 5Eshows the nucleic acid and protein sequence for thehPDL1-GPI-P2A-hFGL1-GPI fusion polypeptide wherein the text for thesignaling domain hPDL1 and hFGL1 are bolded, P2A sequence is underlined,and sticky binder GPI is italicized. With P2A included, a self-cleavingpeptide sequence, artificial synapses with this feature will have bothhPDL1-GPI and FGL1-GPI loaded onto the surface. FIG. 5F shows thenucleic acid and protein sequence for the hPDL1-GPI fusion polypeptidewherein the text for the signaling domain hPDL1 is bolded and stickybinder GPI is italicized. FIG. 5G shows the nucleic acid and proteinsequence for the hPDL1-Fc-GPI fusion polypeptide wherein the text forthe signaling domain hPDL1 is bolded, Fc is underlined, and stickybinder GPI is italicized. FIG. 5H shows the nucleic acid and proteinsequence for the hPDL2-Fc-GPI fusion polypeptide wherein the text forthe signaling domain hPDL2 is bolded, Fc is underlined, and stickybinder GPI is italicized. FIG. 5I shows the nucleic acid and proteinsequence for the hPDL1-C1C2 fusion polypeptide wherein the text for thesignaling domain hPDL1 is bolded and sticky binder C1C2 is italicized.FIG. 5J shows the nucleic acid and protein sequence for the hPDL2-C1C2fusion polypeptide wherein the text for the signaling domain hPDL2 isbolded and sticky binder C1C2 is italicized. FIG. 5K shows the nucleicacid and protein sequence for the 4F2-h41BBL fusion polypeptide whereinthe text for the signaling domain h41BBL is bolded and sticky binder 4F2is italicized. FIG. 5L shows the nucleic acid and protein sequence forthe hPDL1-4Fc-GPI fusion polypeptide wherein the text for the signalingdomain hPDL1 is bolded, 4Fc is underlined, and sticky binder GPI isitalicized. FIG. 5M shows the nucleic acid and protein sequence for theMyr-NanoLuc Luciferase fusion polypeptide wherein the text for thesignaling domain NanoLuc Luciferase is bolded, and sticky binder Myr isitalicized. FIG. 5N shows the nucleic acid and protein sequence for theMyr-mScarlet fusion polypeptide wherein the text for the signalingdomain mScarlet is bolded, and sticky binder Myr is italicized. FIG. 5Oshows the nucleic acid and protein sequence for the secreted isoform ofhPDL1 (SecPDL1) fusion polypeptide hSecPDL1-GPI wherein the text for thesignaling domain hSecPDL1 is bolded and sticky binder GPI is italicized.FIG. 5P shows the nucleic acid and protein sequence for the Tfr2-h41BBLfusion polypeptide wherein the text for the signaling domain h41BBL isbolded and sticky binder Tfr2 is italicized. FIG. 5Q shows the nucleicacid and protein sequence for the CD9tm3-h41BBL fusion polypeptidewherein the text for the signaling domain h41BBL is bolded and stickybinder CD9tm3 is italicized. FIG. 5R shows the nucleic acid and proteinsequence for the Myr/Palm-4F2-h41BBL fusion polypeptide wherein the textfor the signaling domain h41BBL is bolded, sticky binder Myr/Palm isunderlined, and sticky binder 4F2 is italicized. FIG. 5S shows thenucleic acid and protein sequence for the Myr/Palm-Link-h41BBL fusionpolypeptide wherein the text for the signaling domain h41BBL is bolded,sticky binder Myr/Palm is italicized and underlined, and sticky binderLink (in this embodiment a GSSG linker) is in regular text (notunderlined and not italicized). FIG. 5T shows the nucleic acid andprotein sequence for the hPDL1-Link-GPI fusion polypeptide wherein thetext for the signaling domain hPDL1 is bolded, Link is underlined (inthis embodiment a GSSG linker), and sticky binder GPI is italicized.FIG. 5U shows the nucleic acid and protein sequence for the secretedisoform of hPDLI (SecPDL1) fusion polypeptide hSecPDL1-CD9tm2 whereinthe text for the signaling domain hSecPDL1 is bolded and sticky binderCD9tm2 is italicized. FIG. 5V shows the nucleic acid and proteinsequence for the secreted isoform of hPDLI (SecPDL1) fusion polypeptidehSecPDL1-CD9tm2-KRAS wherein the text for the signaling domain hSecPDL1is bolded, sticky binder CD9tm2 is italicized, and sticky binder KRAS isitalicized and underlined. FIG. 5W shows the nucleic acid and proteinsequence for the secreted isoform of hPDL1 (SecPDL1) fusion polypeptidehSecPDL1-CD9tm4 wherein the text for the signaling domain hSecPDL1 isbolded and sticky binder CD9tm4 is italicized. FIG. 5X shows the nucleicacid and protein sequence for the secreted isoform of hPDL1 (SecPDL1)fusion polypeptide hSecPDL1-CD81 wherein the text for the signalingdomain hSecPDL1 is bolded and sticky binder CD81 is italicized. FIG. 5Yshows the nucleic acid and protein sequence for the hCD200-Fc-GPI fusionpolypeptide wherein the text for the signaling domain hCD200 is bolded,Fc is underlined, and sticky binder GPI is italicized, a spacer sequencedomain (regular text, not underlined and not italicized) separateshCD200 sequence from the Fc domain, a spacer sequence domain (regulartext, not underlined and not italicized) separates Fc sequence from theGPI. FIG. 5Z shows the nucleic acid and protein sequence for thehFGL1-GPI fusion polypeptide wherein the text for the signaling domainhFGL1 is bolded, and sticky binder GPI is italicized. FIG. 5AA shows thenucleic acid and protein sequence for the hGal9-Fc-GPI fusionpolypeptide wherein the text for the signaling domain hGal9 is bolded,Fc is underlined, and sticky binder GPI is italicized. FIG. 5BB showsthe nucleic acid and protein sequence for the hCD200-GPI fusionpolypeptide wherein the text for the signaling domain hCD200 is bolded,and sticky binder GPI is italicized. FIG. 5CC shows the nucleic acid andprotein sequence for the hGal9-GPI fusion polypeptide wherein the textfor the signaling domain hGal9 is bolded, and sticky binder GPI isitalicized. FIG. 5DD shows the nucleic acid and protein sequence for thehHVEM-GPI fusion polypeptide wherein the text for the signaling domainhHVEM is bolded, and sticky binder GPI is italicized. FIG. 5EE shows thenucleic acid and protein sequence for the hPDL2-GPI fusion polypeptidewherein the text for the signaling domain hPDL2 is bolded, and stickybinder GPI is italicized. FIG. 5FF shows the nucleic acid and proteinsequence for the hTSG6-GPI fusion polypeptide wherein the text for thesignaling domain hTSG6 is bolded, and sticky binder GPI is italicized.FIG. 5GG shows the nucleic acid and protein sequence for thehHVEM-Fc-GPI fusion polypeptide wherein the text for the signalingdomain hHVEM is bolded, Fc is underlined, and sticky binder GPI isitalicized. FIG. 5HH shows the nucleic acid and protein sequence for themCTLA4-Fc-GPI fusion polypeptide wherein the text for the signalingdomain mCTLA4 is bolded, Fc is underlined, and sticky binder GPI isitalicized. FIG. 5II shows the nucleic acid and protein sequence for themPDL1-C1C2 fusion polypeptide wherein the text for the signaling domainmPDL1 is bolded and sticky binder C1C2 is italicized. FIG. 5JJ shows thenucleic acid and protein sequence for the mPDL1-Fc-GPI fusionpolypeptide wherein the text for the signaling domain mPDL1 is bolded,Fc is underlined, and sticky binder GPI is italicized. FIG. 5KK showsthe nucleic acid and protein sequence for the mPDL1-GPI fusionpolypeptide wherein the text for the signaling domain mPDL1 is boldedand sticky binder GPI is italicized. FIG. 5LL shows the nucleic acid andprotein sequence for the mPDL2-C1C2 fusion polypeptide wherein the textfor the signaling domain mPDL2 is bolded and sticky binder C1C2 isitalicized. FIG. 5MM shows the nucleic acid and protein sequence for themPDL2-Fc-GPI fusion polypeptide wherein the text for the signalingdomain mPDL2 is bolded, Fc is underlined, and sticky binder GPI isitalicized. FIG. 5NN shows the nucleic acid and protein sequence for themPDL1-mFc-GPI fusion polypeptide wherein the text for the signalingdomain mPDL2 is bolded, mFc is underlined, and sticky binder GPI isitalicized. FIG. 5OO shows the nucleic acid and protein sequence for themPDL2-GPI fusion polypeptide wherein the text for the signaling domainmPDL2 is bolded and sticky binder GPI is italicized. FIG. 5PP shows thenucleic acid and protein sequence for the mPDL1-GPI-P2A-mHVEM-GPI fusionpolypeptide wherein the text for the signaling domain mPDL1 and mHVEMare bolded, P2A sequence is underlined, and sticky binder GPI isitalicized. With P2A included, a self-cleaving peptide sequence,artificial synapses with this feature will have both mPDL1-GPI andmHVEM-GPI loaded onto the surface. FIG. 5QQ shows the nucleic acid andprotein sequence for the hPDL1-ADAM10 fusion polypeptide wherein thetext for the signaling domain mPDL1 is bolded and sticky binder ADAM10is italicized. FIG. 5RR shows the nucleic acid and protein sequence forthe hPDLI-4Fc-CD9tm2 fusion polypeptide wherein the text for thesignaling domain hPDL1 is bolded, 4Fc is underlined, and sticky binderCD9tm2 is italicized. FIG. 5SS shows the nucleic acid and proteinsequence for the fusion polypeptide hPDL1-4Fc-CD9tm2-KRAS wherein thetext for the signaling domain hPDL1 is bolded, sticky binder 4Fc isunderlined, sticky binder CD9tm2 is italicized, and sticky binder KRASis italicized and underlined. FIG. 5TT shows the nucleic acid andprotein sequence for the hPDL1-Fc-CD9tm2 fusion polypeptide wherein thetext for the signaling domain hPDL1 is bolded, Fc is underlined, andsticky binder CD9tm2 is italicized. FIG. 5UU shows the nucleic acid andprotein sequence for the fusion polypeptide hPDL1-Fc-CD9tm2-KRAS whereinthe text for the signaling domain hPDL1 is bolded, sticky binder Fc isunderlined, sticky binder CD9tm2 is italicized, and sticky binder KRASis italicized and underlined. FIG. 5VV shows the nucleic acid andprotein sequence for the mPDL1-mFc-CD9tm2 fusion polypeptide wherein thetext for the signaling domain mouse PDL1 (mPDL1) is bolded, mouse mFc(mFc) is underlined, and sticky binder CD9tm2 is italicized. FIG. 5WWshows the nucleic acid and protein sequence for the fusion polypeptidemPDL1-mFc-CD9tm2-KRAS wherein the text for the signaling domain mPDL1 isbolded, sticky binder mFc is underlined, sticky binder CD9tm2 isitalicized, and sticky binder KRAS is italicized and underlined. WhereinmPDL1 and mFc are mouse PDL1 and mouse Fc, respectively.

FIG. 6 shows hPD-L1-Fc-GPI artificial synapse purification via amultimodal resin marketed for exosome purification. Large MW artificialsynapses elute in the first fraction as shown by the high hPD-L1concentration and artificial synapse quantity (2.26E9 synapses/ml) inelution 1. Clean in place (CIP) fractions show bound and eliminatedproteins from the Inventors' artificial synapse elution.

FIG. 7 shows hPDL1-Fc-GPI exosome purification via size exclusionchromatography using a resin marketed for exosome purification.Artificial synapses engineered from exosomes eluted from via amultimodal resin may be further purified via size exclusionchromatography using a resin marketed for exosome purification as shownhere. Using a size exclusion chromatography, artificial synapses elutein fractions 7-9. Total protein (determined by qBit) and hPD-L1 ng/ml(determined by ELISA) of each fraction is shown in the graph. Bars showexosome number per ml (i.e., 1E10 exosomes/ml etc.). Fractions 7-9contain >99% purified artificial synapses. Fractions 7-9 are pooled andmay be concentrated using a filtration device, for example a 10K MWCOAmicon centrifugal filter. Final purified product may be filteredthrough a low protein binding filter, for example a 0.2 μm or 0.45 μmPES filter.

FIG. 8 shows hPD-L1 Expression on exosomes, quantity and hPD-L1concentration was determined in size exclusion chromatography fractions7-9. Knowing the molecular weight of engineered hPD-L1, the Inventorscan determine the number of hPD-L1 molecules per exosome to beapproximately between 12 and 40 hPD-L1/exosome. This value is consistentbetween different purification runs and constructs.

FIG. 9 shows the purification of hPD-L2-Fc-GPI artificial synapsesengineered from exosomes via multimodal resin marketed for exosomepurification. This graph shows Abs 280 of fractions and quantity ofhPDL2 in indicated fractions. Exosomes eluted in Elution 1. Clean inplace (CIP) fractions show bound and eliminated proteins from theInventors' artificial synapse elution.

FIG. 10 shows purification of hPD-L2-Fc-GPI labeled exosomes via sizeexclusion column as shown here using size exclusion resin marketed forexosome purification. Fractions containing large molecular weightexosomes (Fractions 7-9) showed high hPD-L2 concentration indicatingthat the purified exosomes contain hPD-L2-Fc-GPI. Total protein(determined by qBit) and hPD-L1 ng/ml (determined by ELISA) of eachfraction is shown in the graph. Lower molecular weight unboundhPD-L2-Fc-GPI eluted at later fractions.

FIG. 11 shows hCTLA-4-Fc-GPI exosome purification via size exclusioncolumn as shown here using size exclusion resin marketed for exosomepurification. Using size exclusion chromatography, exosomes elute infractions 7-9. Total protein (determined by qBit) and hCTLA4 ng/ml(determined by ELISA) of each fraction is shown in the graph. Fractions7-9 are pooled and contain >99% purified exosomes. Pooled exosomefractions may then be concentrated using a filtration device, forexample a 10K MWCO Amicon centrifugal filter. Final purified product maybe filtered through a low protein binding filter, for example a 0.2 μmor 0.45 urn PES filter. Knowing the molecular weight of engineeredhCTLA-4, the Inventors can determine the number of hCTLA-4 molecules perexosome to be approximately 233 hCTLA-4/exosome.

FIG. 12A shows PD-1 Signaling Bioassay Method. The Inventors establisheda method to validate that PD-L1 and PD-L2 artificial synapses engineeredfrom exosomes can bind to cells expressing PD-1 ligand. To perform thisvalidation method, the Inventors modified the PathHunter PD-1 SignalingBioassay from DiscoverX Briefly, the PathHunter PD-1 Signaling Bioassayrelies on the well-established PathHunter Enzyme FragmentComplementation (EFC) technology to interrogate receptor activity. EFCconsists of a split β-galactosidase (β-gal) enzyme: the Enzyme Donor(ED) and Enzyme Acceptor (EA) fragments which independently have noβ-gal activity. However, when forced to complement they form an activeβ-gal enzyme that will hydrolyze substrate to produce a chemiluminescentsignal. The PathHunter PD-1 Signaling Bioassay consists of human cellsengineered to stably express an ED-tagged PD-1 receptor, while EA isfused to the phosphotyrosine-binding SH2 domain of the intracellularsignaling protein, SHP1. Ligand or antibody-induced activation of thereceptor results in phosphorylation of the receptor's cytosolic tail.Ligand engagement, through addition of ligand-presenting artificialsynapses engineered from exosomes, results in phosphorylation of PD-1,leading to the recruitment of SHP1-EA. This forces complementation ofthe EFC components to create an active β-gal enzyme. This active enzymehydrolyzes substrate to create chemiluminescence as a measure ofreceptor activity. Addition of an antagonist (e.g., antibody to PD-L1)blocks PD-1 signaling, and will prevent complementation, resulting in aloss of signal. FIG. 12B shows that the Inventors obtained approximately10,000× higher increase in Relative Light Units (RLU) in Jurkatsignaling cells treated with PD-L1 or PD-L2 labeled artificial synapseswhen compared to soluble PD-L1-Fc or PD-L2-Fc ligand, respectively.Meaning, it took 10,000× less ug/ml of PD-L1 or PD-L2 on artificialsynapses than solubilized PD-L1-Fc or PD-L2 ligand to achieve the sameRLU signaling. Shown is a dose-response curve for the PD-L1 and PD-L2artificial synapses engineered from exosomes vs soluble PD-L1 and PD-L2signaling bioassay.

FIG. 13A-13C shows experimental EAU outline Test Agent A—unmodifiedexosomes, Test Agent B—mPDL1-Fc-GPI artificial synapses engineered fromexosomes 40 ug/ml, Test Agent C—mPDL1-Fc-GPI artificial synapsesengineered from exosomes 400 ug/ml, IRBP—interphotoreceptorretinoid-binding protein (IRBP) peptide, BID—Bis in die (2× daily)p.o.—Per os (orally) (FIG. 13B) EAU symptoms appear at day 6. 1stintravitreal injection and 2nd intravenous injections are performed onDay 6. There is a statistically significant initial reduction in EAU inmouse PD-L1 (mPD-L1) artificial synapses engineered from exosomestreated rats via either the intravitreal and intravenous delivery modes.2nd intravitreal and 3rd intravenous injections are performed on Day 12.There appears to be a more rapid rate of resolution in the 1×intravitreal and intravenous groups. (FIG. 13C) Weight of rats wasmonitored throughout the study. 3rd intravitreal and 4th intravenousinjections are performed on Day 16. There does not appear to be anysignificant change in EAU in any of the test groups. The aforementionedresults provide proof of principle of successfully treating anautoimmune condition (i.e. EAU) with human cell derived artificialsynapses with PD-L1.

FIG. 14 shows 2 types of ligands displayed on the exosome surface (TypeI and Type II membrane proteins). Type I membrane proteins wherein theN-Terminus is on the luminal (interior) side of the exosome membrane andthe C-Terminus is on the exterior of the exosome.

Type II membrane proteins wherein the N-Terminus is on the exteriorwhile the C-Terminus is on the interior.

FIG. 15 shows a schematic representation of several embodiments of TypeI membrane protein constructs, which include but are not limited to:PD-L1, PD-L2, FGL1, OX40L.

FIG. 16 shows a schematic representation of several embodiments of thesurface of an extracellular vesicle engineered with a Type I membraneprotein of interest (POI) with a variable membrane anchor. Vesicletargeting sequences such as select sequences from 4F2 (CD98), ADAM10,CD298, TFR2, transmembrane portions of CD9, MARCKS, KRAS, and GPI fromCD55. Proteins engineered to include a targeting sequence domain mayinclude one or more linkers between the sticky binder and signalingdomain (e.g., an Fc linker or a bond sequence wherein the bond sequencemay be dimerization or multimerization sequence).

FIG. 17 shows a schematic representation of the surface of an exosomeengineered with an extracellular portion of the Type II membrane proteinof interest (POI) with transmembrane/exosome targeting domains.

FIG. 18 shows a schematic representation of an exosome engineered withan extracellular portion of the Type II membrane protein 4-1BB.

FIG. 19 demonstrates a construct design for labeling an exosome surfacewith Type II membrane proteins.

FIG. 20 shows a schematic representation of a construct design forlabeling an exosome surface with multiple POI domains operably linked bya cleavable (e.g., P2A) linker.

FIG. 21 shows a flow chart of purification and analytical processesprovided herein.

FIG. 22 shows a PD-L1 labeled exosome constructs.

FIG. 23 shows several embodiments of the surface of an exosomeengineered with PD-L1. The PD-L1 can be the membrane-bound PD-L1 isotypeor secreted PD-L1 (SecPD-L1).

FIG. 24 demonstrates size exclusion chromatography for purifying humanPD-L1-GPI (no Fc) exosomes. Left panel: Protein, RNA and DNAmeasurements in SEC fractions are shown. Invitrogen Qubit fluorometricassays were used to measure biomolecules from unmodified concentratedcell media SEC fractions or hPD-L1-Exo-Tag concentrated cell media SECfractions. PD-L1 was measured using an R&D systems PD-L1 ELISA kit.Right panel shows dot-blot immunoblot analysis of SEC fractions. A96-well dot blot apparatus was used to immobilize 50 ul of each SECfraction onto PVDF. Right bottom figures: Exosome size and concentrationwas measured in fraction 7 by tunable resistive pulse sensing (TRPS).

FIG. 25 demonstrates that GPI anchors hPD-L1 on exosomes.

FIG. 26 demonstrates that a multimodal resin marketed for exosomepurification purifies and disaggregates exosomes.

FIG. 27 shows the exosome decoration with hPD-L1-Fc-GPI.

FIG. 28A shows the exosome decoration with hPD-L1-Fc-GPI. Fraction 7contained the purified hPD-L1-Fc-GPI vesicles. FIG. 28B shows sizeexclusion chromatography (SEC) purification results of variousembodiments of human PD-L1 displayed on the surface of extracellularvesicles.

FIG. 29 shows that mouse PD-L1-Fc-GPI exosomes have higher valency thanmPD-L1-GPI.

FIG. 30A-30C demonstrates comparison proteomics of transproteinexpression and shows that surface labeling on the engineeredextracellular vesicles provided herein do not affect the relativeexpression of native and associated exosome proteins. FIG. 30A showshPD-L1-Fc-GPI. FIG. 30B shows hPD-L2-FcGPI. FIG. 30C showshCTLA4-Fc-GPI.

FIG. 31 shows production of mPD-L1-Fc-GPI in STR Bioreactor.

FIG. 32 shows purification of mPD-L1-Fc-GPI (STR) via SEC. Graph showsmPD-L1 ng/ml vs Total Protein ug/ml.

FIG. 33 shows purification mPDL1-Fc-GPI (STR bioreactor).

FIG. 34 shows a schematic representation of the 4-1BBL labeled exosomes.Top: Vector map showing the N-terminal cystolic domain, a transmembrane(TM) domain, and the POI domain at the C-terminus. Bottom: An embodimentof an engineered EV with a type-II membrane display of the fusionprotein.

FIG. 35 shows embodiments of a 4-1BBL display exosome.

FIG. 36A-36B show the protein engineering and purification of 4F2-4-1BBLlabeled exosomes. FIG. 36B confirms that h4-1BBL is displayed on theengineered exosomes.

FIG. 37 shows internal fusion protein loading of exosomes.

FIG. 38 shows internal loading of exosomes with mScarlet (RFP).

FIG. 39A shows internal loading of exosomes with NanoLuc luciferase.FIG. 39B shows tetraspanin characterization of exosomes internallyloaded with NanoLuc luciferase.

FIG. 40A shows the mechanism of PD-L1 engineered extracellular vesiclesinduce membrane clustering and receptor agonism on a target cell. Anexemplary model of proposed mechanism of extracellular vesicles with aType I membrane protein signaling domain (PD-L1) promoting receptorclustering on a target cell, wherein receptor clustering promotesincreased potency of signal transduction of the target receptor.Antagonist antibodies function well at blocking receptors. Antibodiesare poor agonist modalities due to their general inability to clusterreceptors. Ligands on a membrane surface are potent agonists, howeverthe cost and cold chain logistics of cell therapies makescommercialization difficult and expensive. Extracellular vesiclesengineered with Type I membrane protein are able to induce receptorclustering of target receptors and initiate and propagate a potentsignal response on a target cell.

FIG. 40B shows the mechanism of 4-1BBL engineered extracellular vesiclesinduce membrane clustering and receptor agonism on a target cell. Anexemplary model of proposed mechanism of extracellular vesicles with aType II membrane protein signaling domain (4-1BBL) promoting receptorclustering on a target cell, wherein receptor clustering promotesincreased potency of signal transduction of the target receptor. Solubleligands are often poor agonist modalities due to their general inabilityto cluster receptors. Ligands displayed on a membrane surface are potentagonists, however the cost and cold chain logistics of cell therapiesmakes commercialization difficult and expensive. Extracellular vesiclesengineered with Type II membrane protein are able to induce receptorclustering of target receptors and initiate and propagate a potentsignal response on a target cell.

DETAILED DESCRIPTION

The compositions and methods provided herein are based, in part, on thediscovery that engineered extracellular vesicles (e.g., exosomes)expressing an engineered fusion protein (e.g., PD-L1) reducesinflammation in an animal model of experimental autoimmune uveoretinitis(EAU), an autoimmune disorder. The compositions and methods providedherein are further based, in part, on the discovery that engineeredextracellular vesicles produce enhanced signaling compared to an equalquantity of recombinant ligand. Since some cellular receptors, (e.g.,PD-1) require clustering or super-clustering to promote a signalingresponse, it stands to reason that extracellular vesicles engineered toexpress ligands on their surface wherein the ligands may engage targetreceptors on target cells and promote clustering of said targetreceptors thereby promoting a signal response on said target cell.

In one aspect, provided herein is an engineered extracellular vesiclecomprising: at least one fusion polypeptide comprising: at least oneprotein of interest (POI) domain; and at least one vesicle targetingdomain. In some embodiments of any of the aspects, the engineeredextracellular vesicle is an exosome. In some embodiments, of any of theaspects, the fusion protein further comprises at least one linker. Insome embodiments of any of the aspects, the POI domain can substantiallybind to a target polypeptide. In some embodiments of any of the aspectsprovided herein, the engineered extracellular vesicle is an artificialsynapse.

Generally, the extracellular vesicles (e.g., exosomes) provided hereinare produced by contacting a population of cells with a nucleic acidconstruct encoding the fusion proteins provided herein and isolating aplurality of extracellular vesicles. The extracellular vesicles can thenbe purified by methods provided herein and are formulated fortherapeutic use, including but not limited to, for the treatment ofautoimmune diseases, cancer, or modulating inflammation in a subject.

The compositions and methods provided herein are specifically designedto exploit the membrane trafficking mechanisms of extracellular vesiclesand rely on the hallmark biophysical and biochemical properties ofextracellular vesicles, such as exosomes. The vesicles/artificialsynapses provided herein are specifically engineered to induce/agonizeand propagate biological signaling via a target polypeptide (e.g., byactivating a receptor or enzyme or agonizing said receptor or enzyme).Alternatively, the engineered extracellular vesicles provided herein canact as cellular decoys or to reduce or antagonize biological signaling,e.g., by blocking an endogenous ligand from binding to a target cellularreceptor and preventing activation of the receptor.

Engineering of the extracellular vesicles provided herein extends thesecapabilities significantly by incorporating sticky binders attaching toextracellular vesicles such as exosomes, further coupled with signalingdomains of choice. For example, attachment of sticky binders toexosomes, along with their linked signaling domains, allows for receptorclustering for biological signal induction/agonism and propagation nototherwise possible. In this aspect, the aforementioned design achievesthe aim of an engineered extracellular vesicle by inducing the desiredbiological signaling in a target recipient cell.

Various aspects and embodiments of the compositions and methods areprovided herein in detail below.

Engineered Extracellular Vesicle (EV) Compositions

The compositions provided herein comprises at least one extracellularvesicle (also termed artificial synapse or abbrv: EV), wherein theextracellular vesicle comprises at least one fusion polypeptide or aplurality of fusion polypeptides comprising: at least one vesicletargeting domain (e.g., sticky binders); and at least one protein ofinterest domain or a fragment thereof (also termed signaling domains).

Extracellular vesicles (EVs) are lipid particles that are released fromvarious cell types that function to transfer “cargo” such as nucleicacids and proteins to other cells. EVs are not able to replicate butserve as cell messengers. EV-mediated signals can be transmitted by allthe different biomolecule categories—protein, lipids, nucleic acids andsugars—and the unique package of this information provides bothprotection and the option of simultaneous delivery of multiple differentmessengers even to sites remote to the vesicular origin. See, e.g.,Yáñez-Mó M, Siljander P R, Andreu Z, et al. Biological properties ofextracellular vesicles and their physiological functions. J ExtracellVesicles. 2015; 4:27066. Published 2015 May 14.doi:10.3402/jev.v4.27066, which is incorporated herein by reference inits entirety. Furthermore, there is an increasing amount of evidencethat shows that EVs can modulate a milieu of cellular signalingprocesses. See, e.g., Yadid et al. Science Translation Medicine (2020);Cerqueira de Abreu et al. Nature Reviews Cardiology (2020); Zhang W. etal. Protein J. (2019); Zha Q B et al. Tumor Biology. February 2017; Tanet al. (2016) Recent advances of exosomes in immune modulation andautoimmune diseases, Autoimmunity, 49:6, 357-365; Kalluri R, LeBleu V S.et al. The biology, function, and biomedical applications of exosomes.Science. 2020 Feb. 7; 367(6478); which is incorporated herein byreference in its entirety.

There are various types of extracellular vesicles that are named fortheir site of origin in a cell, size, and structural and/or functionalproperties. In some embodiments of any of the aspects provided herein,the extracellular vesicle is an exosome, ectosome, macrovesicle,microparticle, apoptotic body, vesicular organelle, oncosome, exosphere,exomeres, or cell derived nanovesicle (CDN) ((e.g., by genesis viagrating or shearing cells), liposomes or the like known by one ofordinary skill in the art. In various embodiments, the extracellularvesicle comprises a phospholipid bilayer with an exterior phospholipidlayer and an interior phospholipid layer, wherein the exteriorphospholipid layer has an external surface and an internal surface,wherein the interior phospholipid layer has an internal surface and anexternal surface, and the internal surface of the exterior phospholipidlayer faces the internal surface of the interior phospholipid layer, andthe phospholipid bilayer encloses an internal space, wherein theexternal surface of the interior phospholipid layer faces the internalspace and wherein the external surface of the exterior phospholipidlayer faces an extracellular environment, and the external surface ofthe inner phospholipid layer is the internal surface of theextracellular vesicle.

In various embodiments, the extracellular vesicles range in size from 30nanometers (nm) to 300 nm. In various embodiments, the plurality of EVsrange in size from about 30 nm to about 150 nm. In various embodiments,the plurality of EVs or artificial synapses includes one or moreartificial synapses that are about 10 nm to about 250 nm in diameter,including those about 10 nm to about 15 nm, about 15 nm to about 20 nm,about 20 nm to about 25 nm, about 25 nm to about 30 nm, about 30 nm toabout 35 nm, about 35 nm to about 40 nm, about 40 nm to about 50 nm,about 50 nm to about 60 nm3 about 60 nm to about 70 nm, about 70 nm toabout 80 nm, about 80 nm to about 90 nm, about 90 nm to about 95 nm,about 95 nm to about 100 nm, about 100 nm to about 105 nm, about 105 nmto about 110 nm, about 110 nm to about 115 nm, about 115 nm to about 120nm, about 120 nm to about 125 nm, about 125 nm to about 130 nm, about130 nm to about 135 nm, about 135 nm to about 140 nm, about 140 nm toabout 145 nm, about 145 nm to about 150 nm, about 150 to about 200 nm,about 200 nm to about 250 nm, about 250 nm or more.

In some embodiments of any of the aspects provided herein, the EV is anexosome. Exosomes are membrane-bound EVs that are produced in theendosomal compartment of most eukaryotic cells. As used herein, the term“exosome” refers to a species of extracellular vesicle between about 20nm to about 400 μM in diameter, e.g, about 30 nm-200 nm in diameter byinward invagination of a portion of a membrane of an endosome (forexample an early or late endosome), wherein the endosome is within acell comprising a plasma membrane, and the exosome is released from thecell upon fusion of another portion of the endosome membrane with theplasma membrane. An exosome may refer to a species of extracellularvesicle between 20 nm-400 μM in diameter, more preferably 30 nm-200 nmin diameter, that originates by budding of a portion of a plasmamembrane from a cell wherein the budded portion of the plasma membraneis released to the extracellular environment.

The EVs (e.g., exosomes or cell derived vesicles) provided herein maycomprise cargo, for example, peptides, proteins, nucleic acids, lipids,metabolites, carbohydrates, biomolecules, small molecules, largemolecules, vesicles, organelles, or fragments thereof. Exosome cargo maybe located within the internal space of the exosome. EV cargo may bemembrane bound spanning one or both layers of the exosome phospholipidbilayer (for example a transmembrane protein). EV cargo may be incontact with the exterior or interior surface of the exosome, forexample through a covalent bond or a non-covalent bond. The phospholipidbilayer of the EV or exosome provided herein may comprise one or moretransmembrane proteins, wherein a portion of the one or moretransmembrane membrane proteins is located within the internal space ofthe exosome. The phospholipid bilayer of the EV or exosome providedherein may comprise one or more transmembrane proteins, wherein aportion of the one or more transmembrane membrane proteins traverses theEV phospholipid bilayer. The phospholipid bilayer of the EV may compriseone or more transmembrane proteins, wherein the one or moretransmembrane membrane proteins comprises a domain on the exterior ofthe exosome.

In some embodiments of any of the aspects, the extracellular vesicles orexosomes provided herein endogenously express CD81+, CD82+, CD37+,CD63+, CD9+, CD151+, CD105+, or any combination thereof. In variousembodiments, the plurality of artificial synapses includes one or moreartificial synapses expressing a biomarker. In certain embodiments, thebiomarkers are tetraspanins. In other embodiments, the tetraspanins areone or more selected from the group including CD63, CD81, CD82, CD53,CD151, and CD37. In other embodiments, the artificial synapses expressone or more lipid raft associated proteins (e.g.,glycosylphosphatidylinositol-anchored proteins and flotillin),cholesterol, sphingolipids such as sphingomyelin, and/orhexosylceramides.

In other embodiments, the biological protein is related to exosomeformation and packaging of cytosolic proteins, e.g., Hsp70, Hsp90,14-3-3 epsilon, PKM2, GW182 and AGO2. In certain embodiments, theartificial synapses express CD63, HSP70, CD105 or combinations thereof.In other embodiments, the artificial synapses do not express CD9 orCD81, or express neither. For example, plurality of artificial synapsescan include one or more artificial synapses that are CD63+, HSP+,CD105+, CD9−, and CD81−.

The EVs provided herein are specifically engineered to express fusionpolypeptides that elicit biological signaling via a target cell. In someembodiments, the fusion polypeptide is overexpressed to elicit abiological response on a target cell or target polypeptide. Theengineered EV comprises at least one fusion polypeptide and can comprisea plurality of the same or different fusion polypeptides providedherein. The fusion polypeptides provided herein comprise a protein ofinterest domain, also termed the signaling domain.

The fusion polypeptides provided herein can comprise one or more of aprotein of interest domain, such that expression of said fusionpolypeptide is permitted and that the number of POI domains does notimpede protein expression or folding. Furthermore, the EVs providedherein can express more than one fusion protein (e.g., encoded bymultiple different nucleic acid constructs). One of skill in the art canappreciate that an engineered EV can include one or more combinations ofdifferent signaling domains and/or vesicle targeting domains, or thatone can use a plurality of engineered EVs, each including one or morevesicle targeting domains and one or more signaling domains.

In some embodiments, the EVs provided herein comprise one or more, twoor more, three or more, four or more, five or more, six or more, sevenor more, eight or more, nine or more, or ten or more fusion proteins.The fusion proteins can be encoded by the same vector or separatevectors. In some embodiments of any of the aspects, the engineeredextracellular vesicle comprises at least two POI domains and/or at leasttwo vesicle targeting domains.

In some embodiments, the fusion polypeptide comprises one or more, twoor more, three or more, four or more, five or more, or six or more POIdomains on the same polypeptide or nucleic acid construct encoding saidpolypeptide. For example, the fusion polypeptides provided herein canexpress a fusion polypeptide encoding one or more, two or more, three ormore, four or more, five or more, or six or more signaling domains. Inanother example, the fusion polypeptides provided herein can express afusion polypeptide encoding an immune checkpoint protein or a proteininvolved in immune or cell synapse or any combination or fragmentthereof.

In some embodiments, the EV comprises one or more, two or more, three ormore, four or more, five or more, or six or more fusion polypeptides onthe same EV. For example, EVs comprising one or more, two or more, threeor more, four or more, five or more, or six or more fusion polypeptideswherein the fusion polypeptides encode a signaling domain. In anotherexample, EVs comprising one or more, two or more, three or more, four ormore, five or more, or six or more fusion polypeptides wherein thefusion polypeptides encode for one or more immune checkpoint proteins orproteins involved in immune or cell synapse, or any combination orfragment thereof.

In various embodiments, the signaling domain is a protein or peptide ofinterest, or a fragment thereof. In various embodiments, the protein ofinterest (signaling domain) is an immune checkpoint protein. The terms“immune checkpoint protein” or “protein involved in immune or cellsynapse” can include but are not limited to adenosine A2A receptor(A2AR), Galectin 9, fibrinogen-like protein 1 (FGL-1), plateletendothelial adhesion factor-1 (PECAM-1), tumor necrosis factor gene 6protein (TSG-6), Stabilin-1 (STAB-1) also known as Clever-1, Neuropilin1 (NRP1), Neuropilin 2 (NRP2), semaphorin-3A (SEMA3A), semaphorin-3F(SEMA3F), repulsive guidance molecule B (RGMB) also known as DRG11,T-cell immunoglobulin and mucin domain 3 (TIM-3), T cell immunoreceptorwith Ig and ITIM domains (TIGIT), human leukocyte antigen (HLA) class I,HLA class II, high mobility group protein B1 (HMGB1),phosphatidylserine, carcinoembryonic antigen-related cell adhesionmolecule 1 (CEACAM-1), T-cell receptor (TCR), Src homology 2domain-containing protein tyrosine phosphatase 1 (SHP-1), SHP-2, F-Boxprotein 38 (FBXO38), signaling lymphocytic activation molecule(SLAM)-associated protein (SAP) also known as SH2D1A, B7RP1, indoleamine2,3-dioxygenase (IDO), NADH oxidase 2 (NOX2), tumor necrosis factorreceptor (TNFR) superfamily member 18 (TNFRSF18) (also known asactivation inducible TNFR family receptor (AITR), glucocorticoid-inducedTNFR related (GITR) protein, and CD357), B7-H4 also known as V-setdomain containing T-cell activator inhibitor (VTCN1), B7-H5 (also knownas V-domain Ig suppressor of T-cell activation (VISTA), plateletreceptor Gi24, and stress induced secreted protein 1 (SISP1), B7-H6(also known as NCR3LG1), B7-H7 (also known as human endogenousretrovirus-H (HERV-H) long terminal repeat-associating protein 2(HHLA2), apelin receptor (APLNR), interferon gamma (IFN y) receptor,programmed cell death-1 (PD-1), Protein Wnt-5a (WNTSA),serine/threonine-protein kinase PAK4, interleukin 6 (IL-6),interleukin-10 (IL-10), NKG2 family of C-type lectin receptors (forexample NKG2A, B, C, D, E, F and H), ligands of NKG2 family, killer cellimmunoglobulin-like receptors, CD-2, cluster of differentiation 4 (CD4),CD8, CD27, CD27 ligand (CD27L, also known as CD70), CD28, CD28H (alsoknown as transmembrane and immunoglobulin domain containing 2 (TMIGD2)and Ig containing and proline-rich receptor-1 (IGPR1)), CD39, CD40,CD44, integrin associated protein (CD47), carcinoembryonic antigenrelated cell adhesion molecule 1 (CEACAM1 also known as CD66a), CD73,B7-1 (also known as CD80), B7-2 (also known as CD86), CD94, CD96,immunoglobulin superfamily member 2 (IGSF2) also known as CD101, nectincell adhesion molecule 2 (NECTIN2) (also known as herpesvirus entrymediator B (HVEB), poliovirus receptor related 2 (PRR2, PVRL2 and PVRR2)and CD112), poliovirus receptor related immunoglobulin domain containingprotein (PVIRG) also known as CD112R, CD122 (also known as IL5RB andP70-75), OX40 (also known as tumor necrosis factor receptor superfamilymember 4 (TNFRSF4) and CD134), OX40 ligand (OX40L), 4-1BB (also known asCD137), CD134 (also known as 4-1BB ligand (4-1BBL) and as tumor necrosisfactor ligand superfamily member 9 (TNFSF9) and CD137L), cytotoxicT-lymphocyte-associated protein 4 (CTLA-4) also known as CD152, CD154(also known as CD40L), poliovirus receptor (PVR) also known as CD155,killer-cell immunoglobulin-like receptors (KIRs) (for example but notlimited to CD158 family, CD158a, CD158g, CD158h, KIR2DL1, KIR2DS1,KIRDS3, and KIR2DS5), CD160, signal-regulatory protein alpha (SIRPα)also known as CD172a, OX-2 also known as CD200, CD200R,lymphocyte-activation gene 3 (LAG-3) also known as CD223, CD226, OX40Lalso known as CD252, herpes virus entry mediator (HVEM) also known astumor necrosis factor receptor superfamily member 14 (TNFRSF14) andCD270, B- and T-lymphocyte attenuator (BTLA) also known as CD272,programmed cell death ligand-2 (PD-L2) (also known as B7-DC, PDCD1LG2,and CD273), programmed cell death-ligand 1 (PD-L1) (also known as B7-H1and CD274), B7-H2 (also known as inducible T-cell co-stimulator ligand(ICOSLG), B7RP1, and CD275), B7-H3 also known as CD276, inducible T-cellco-stimulator (ICOS) also known as CD278, programed cell death protein 1(PD-1) also known as CD279, leukocyte-associated Ig-like receptor-1(LAIR-1) also known as CD305, collagen family of proteins (for examplebut not limited to collagen I, collagen II, collagen III alpha 1,collagen IV, collagen XXIII alpha 1, collagen XXV alpha 1), sialicacid-binding immunoglobulin-type lectin 7 (SIGLEC7) also known as CD328,sialic acid-binding immunoglobulin-type lectin 7 (SIGLEC9) also known asCD329, natural cytotoxicity triggering receptor 3 (NKp30) also known asCD337, or any isoform, fragment, variation thereof, or a ligand to theaforementioned proteins thereof, or the like known by one of ordinaryskill in the art. All variants are encompassed by the present invention.

In some embodiments of any of the aspects provided herein, the proteinof interest domain (POI domain) comprises a polypeptide or a fragmentthereof or a nucleic acid encoding said polypeptide or fragment thereofselected from the group consisting of: Table 1 (below). Non-limitingexamples of nucleic acid sequences that encode the POI domains providedherein are also provided in Table 1.

TABLE 1 Type I Proteins of Interest Amino Acid Sequence Protein ofTranscript Sequence (SEQ ID NO:) InterestAmino Acid Sequence (SEQ ID NO:) Human>NM_014143.4 Homo sapiens CD274 molecule (CD274), Programmedtranscript variant 1, mRNA death-ligand 1AGTTCTGCGCAGCTTCCCGAGGCTCCGCACCAGCCGCGCTTCTGTCCGCCTGCAGGG (PD-L1)CATTCCAGAAAGATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGGACTCACTTGGTAATTCTGGGAGCCATCTTATTATGCCTTGGTGTAGCACTGACATTCATCTTCCGTTTAAGAAAAGGGAGAATGATGGATGTGAAAAAATGTGGCATCCAAGATACAAACTCAAAGAAGCAAAGTGATACACATTTGGAGGAGACGTAATCCAGCATTGGAACTTCTGATCTTCAAGCAGGGATTCTCAACCTGTGGTTTAGGGGTTCATCGGGGCTGAGCGTGACAAGAGGAAGGAATGGGCCCGTGGGATGCAGGCAATGTGGGACTTAAAAGGCCCAAGCACTGAAAATGGAACCTGGCGAAAGCAGAGGAGGAGAATGAAGAAAGATGGAGTCAAACAGGGAGCCTGGAGGGAGACCTTGATACTTTCAAATGCCTGAGGGGCTCATCGACGCCTGTGACAGGGAGAAAGGATACTTCTGAACAAGGAGCCTCCAAGCAAATCATCCATTGCTCATCCTAGGAAGACGGGTTGAGAATCCCTAATTTGAGGGTCAGTTCCTGCAGAAGTGCCCTTTGCCTCCACTCAATGCCTCAATTTGTTTTCTGCATGACTGAGAGTCTCAGTGTTGGAACGGGACAGTATTTATGTATGAGTTTTTCCTATTTATTTTGAGTCTGTGAGGTCTTCTTGTCATGTGAGTGTGGTTGTGAATGATTTCTTTTGAAGATATATTGTAGTAGATGTTACAATTTTGTCGCCAAACTAAACTTGCTGCTTAATGATTTGCTCACATCTAGTAAAACATGGAGTATTTGTAAGGTGCTTGGTCTCCTCTATAACTACAAGTATACATTGGAAGCATAAAGATCAAACCGTTGGTTGCATAGGATGTCACCTTTATTTAACCCATTAATACTCTGGTTGACCTAATCTTATTCTCAGACCTCAAGTGTCTGTGCAGTATCTGTTCCATTTAAATATCAGCTTTACAATTATGTGGTAGCCTACACACATAATCTCATTTCATCGCTGTAACCACCCTGTTGTGATAACCACTATTATTTTACCCATCGTACAGCTGAGGAAGCAAACAGATTAAGTAACTTGCCCAAACCAGTAAATAGCAGACCTCAGACTGCCACCCACTGTCCTTTTATAATACAATTTACAGCTATATTTTACTTTAAGCAATTCTTTTATTCAAAAACCATTTATTAAGTGCCCTTGCAATATCAATCGCTGTGCCAGGCATTGAATCTACAGATGTGAGCAAGACAAAGTACCTGTCCTCAAGGAGCTCATAGTATAATGAGGAGATTAACAAGAAAATGTATTATTACAATTTAGTCCAGTGTCATAGCATAAGGATGATGCGAGGGGAAAACCCGAGCAGTGTTGCCAAGAGGAGGAAATAGGCCAATGTGGTCTGGGACGGTTGGATATACTTAAACATCTTAATAATCAGAGTAATTTTCATTTACAAAGAGAGGTCGGTACTTAAAATAACCCTGAAAAATAACACTGGAATTCCTTTTCTAGCATTATATTTATTCCTGATTTGCCTTTGCCATATAATCTAATGCTTGTTTATATAGTGTCTGGTATTGTTTAACAGTTCTGTCTTTTCTATTTAAATGCCACTAAATTTTAAATTCATACCTTTCCATGATTCAAAATTCAAAAGATCCCATGGGAGATGGTTGGAAAATCTCCACTTCATCCTCCAAGCCATTCAAGTTTCCTTTCCAGAAGCAACTGCTACTGCCTTTCATTCATATGTTCTTCTAAAGATAGTCTACATTTGGAAATGTATGTTAAAAGCACGTATTTTTAAAATTTTTTTCCTAAATAGTAACACATTGTATGTCTGCTGTGTACTTTGCTATTTTTATTTATTTTAGTGTTTCTTATATAGCAGATGGAATGAATTTGAAGTTCCCAGGGCTGAGGATCCATGCCTTCTTTGTTTCTAAGTTATCTTTCCCATAGCTTTTCATTATCTTTCATATGATCCAGTATATGTTAAATATGTCCTACATATACATTTAGACAACCACCATTTGTTAAGTATTTGCTCTAGGACAGAGTTTGGATTTGTTTATGTTTGCTCAAAAGGAGACCCATGGGCTCTCCAGGGTGCACTGAGTCAATCTAGTCCTAAAAAGCAATCTTATTATTAACTCTGTATGACAGAATCATGTCTGGAACTTTTGTTTTCTGCTTTCTGTCAAGTATAAACTTCACTTTGATGCTGTACTTGCAAAATCACATTTTCTTTCTGGAAATTCCGGCAGTGTACCTTGACTGCTAGCTACCCTGTGCCAGAAAAGCCTCATTCGTTGTGCTTGAACCCTTGAATGCCACCAGCTGTCATCACTACACAGCCCTCCTAAGAGGCTTCCTGGAGGTTTCGAGATTCAGATGCCCTGGGAGATCCCAGAGTTTCCTTTCCCTCTTGGCCATATTCTGGTGTCAATGACAAGGAGTACCTTGGCTTTGCCACATGTCAAGGCTGAAGAAACAGTGTCTCCAACAGAGCTCCTTGTGTTATCTGTTTGTACATGTGCATTTGTACAGTAATTGGTGTGACAGTGTTCTTTGTGTGAATTACAGGCAAGAATTGTGGCTGAGCAAGGCACATAGTCTACTCAGTCTATTCCTAAGTCCTAACTCCTCCTTGTGGTGTTGGATTTGTAAGGCACTTTATCCCTTTTGTCTCATGTTTCATCGTAAATGGCATAGGCAGAGATGATACCTAATTCTGCATTTGATTGTCACTTTTTGTACCTGCATTAATTTAATAAAATATTCTTATTTATTTTGTTACTTGGTACACCAGCATGTCCATTTTCTTGTTTATTTTGTGTTTAATAAAATGTTCAGTTTAACATCCCA (SEQ ID NO: 1) >NP_054862.1 programmed cell death 1 ligand 1 isoform aprecursor [Homo sapiens]MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPELPLAHPPNERTHLVILGAILLCLGVALTFIFRLRKGRMMDVKKCGIQDTNSKKQSDTHLEET (SEQ ID NO: 2) Mouse PD-L1>NM_021893.3 Mus musculus CD274 antigen (Cd274), mRNAGAAATCGTGGTCCCCAAGCCTCATGCCAGGCTGCACTTGCACGTCGCGGGCCAGTCTCCTCGCCTGCAGATAGTTCCCAAAACATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTTACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATGGAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGGGAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCTCAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGAAATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGCATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCATACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTAATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCACCAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTCAATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACGTTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTGCCTGCAACACATCCTCCACAGAACAGGACTCACTGGGTGCTTCTGGGATCCATCCTGTTGTTCCTCATTGTAGTGTCCACGGTCCTCCTCTTCTTGAGAAAACAAGTGAGAATGCTAGATGTGGAGAAATGTGGCGTTGAAGATACAAGCTCAAAAAACCGAAATGATACACAATTCGAGGAGACGTAAGCAGTGTTGAACCCTCTGATCGTCGATTGGCAGCTTGTGGTCTGTGAAAGAAAGGGCCCATGGGACATGAGTCCAAAGACTCAAGATGGAACCTGAGGGAGAGAACCAAGAAAGTGTTGGGAGAGGAGCCTGGAACAACGGACATTTTTTCCAGGGAGACACTGCTAAGCAAGTTGCCCATCAGTCGTCTTGGGAAATGGATTGAGGGTTCCTGGCTTAGCAGCTGGTCCTTGCACAGTGACCTTTTCCTCTGCTCAGTGCCGGGATGAGAGATGGAGTCATGAGTGTTGAAGAATAAGTGCCTTCTATTTATTTTGAGTCTGTGTGTTCTCACTTTGGGCATGTAATTATGACTGGTGAATTCTGACGACATGATAGATCTTAAGATGTAGTCACCAAACTCAACTGCTGCTTAGCATCCTCCGTAACTACTGATACAAGCAGGGAACACAGAGGTCACCTGCTTGGTTTGACAGGCTCTTGCTGTCTGACTCAAATAATCTTTATTTTTCAGTCCTCAAGGCTCTTCGATAGCAGTTGTTCTGTATCAGCCTTATAGGTGTCAGGTATAGCACTCAACATCTCATCTCATTACAATAGCAACCCTCATCACCATAGCAACAGCTAACCTCTGTTATCCTCACTTCATAGCCAGGAAGCTGAGCGACTAAGTCACTTGCCCACAGAGTATCAGCTCTCAGATTTCTGTTCTTCAGCCACTGTCCTTTCAGGATAGAATTTGTCGTTAAGAAATTAATTTAAAAACTGATTATTGAGTAGCATTGTATATCAATCACAACATGCCTTGTGCACTGTGCTGGCCTCTGAGCATAAAGATGTACGCCGGAGTACCGGTCGGACATGTTTATGTGTGTTAAATACTCAGAGAAATGTTCATTAACAAGGAGCTTGCATTTTAGAGACACTGGAAAGTAACTCCAGTTCATTGTCTAGCATTACATTTACCTCATTTGCTATCCTTGCCATACAGTCTCTTGTTCTCCATGAAGTGTCATGAATCTTGTTGAATAGTTCTTTTATTTTTTAAATGTTTCTATTTAAATGATATTGACATCTGAGGCGATAGCTCAGTTGGTAAAACCCTTTCCTCACAAGTGTGAAACCCTGAGTCTTATCCCTAGAACCCACATAAAAAACAGTTGCGTATGTTTGTGCATGCTTTTGATCCCAGCACTAGGGAGGCAGAGGCAGGCAGATCCTGAGCTCTCATTGACCACCCAGCCTAGCCTACATGGTTAGCTCCAGGCCTACAGGAGCTGGCAGAGCCTGAAAAACGATGCCTAGACACACACACACACACACACACACACACACACACACACACACACCATGTACTCATAGACCTAAGTGCACCCTCCTACACATGCACACACATACAATTCAAACACAAATCAACAGGGAATTGTCTCAGAATGGTCCCCAAGACAAAGAAGAAGAAAAACACCAAACCAGCTCTATTCCCTCAGCCTATCCTCTCTACTCCTTCCTAGAAGCAACTACTATTGTTTTTGTATATAAATTTACCCAACGACAGTTAATATGTAGAATATATATTAAAGTGTCTGTCAATATATATTATCTCTTTCTTTCTTTCTTCCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTTCTTTCTTTCTTTCTTTTTTTCTGTCTATCTGTACCTAAATGGTTGCTCACTATGCATTTTCTGTGCTCTTCGCCCTTTTTATTTAATGTATGGATATTTATGCTGCTTCCAGAATGGATCTAAAGCTCTTTGTTTCTAGGTTTTCTCCCCCATCCTTCTAGGCATCTCTCACACTGTCTAGGCCAGACACCATGTCTGCTGCCTGAATCTGTAGACACCATTTATAAAGCACGTACTCACCGAGTTTGTATTTGGCTTGTTCTGTGTCTGATTAAAGGGAGACCATGAGTCCCCAGGGTACACTGAGTTACCCCAGTACCAAGGGGGAGCCTTGTTTGTGTCTCCATGGCAGAAGCAGGCCTGGAGCCATTTTGGTTTCTTCCTTGACTTCTCTCAAACACAGACGCCTCACTTGCTCATTACAGGTTCTCCTTTGGGAATGTCAGCATTGCTCCTTGACTGCTGGCTGCCCTGGAAGGAGCCCATTAGCTCTGTGTGAGCCCTTGACAGCTACTGCCTCTCCTTACCACAGGGGCCTCTAAGATACTGTTACCTAGAGGTCTTGAGGATCTGTGTTCTCTGGGGGGAGGAAAGGAGGAGGAACCCAGAACTTTCTTACAGTTTTCCTTGTTCTGTCACATGTCAAGACTGAAGGAACAGGCTGGGCTACGTAGTGAGATCCTGTCTCAAAGGAAAGACGAGCATAGCCGAACCCCCGGTGGAACCCCCTCTGTTACCTGTTCACACAAGCTTATTGATGAGTCTCATGTTAATGTCTTGTTTGTATGAAGTTTAAGAAAATATCGGGTTGGGCAACACATTCTATTTATTCATTTTATTTGAAATCTTAATGCCATCTCATGGTGTTGGATTGGTGTGGCACTTTATTCTTTTGTGTTGTGTATAACCATAAATTTTATTTTGCATCAGATTGTCAATGTATTGCATTAATTTAATAAATATTTTTATTTATTAAAAAAAAAAAAAAAAA (SEQ ID NO: 3) >NP_068693.l programmed cell death 1 ligand 1 precursor[Mus musculus] MRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYWEKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCCIISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDHQPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPELPATHPPQNRTHWVLLGSILLFLIVVSTVLLFLRKQVRMLDVEKCGVEDTSSKNRNDTQFEET (SEQ ID NO: 4) Human PD-L2>NM_025239.4 Homo sapiens programmed cell death 1 ligand2 (PCD1LG2), mRNAACTCTCATGTTACGGCAAACCTTAAGCTGAATGAACAACTTTTCTTCTCTTGAATATATCTTAACGCCAAATTTTGAGTGCTTTTTTGTTACCCATCCTCATATGTCCCAGCTAGAAAGAATCCTGGGTTGGAGCTACTGCATGTTGATTGTTTTGTTTTTCCTTTTGGCTGTTCATTTTGGTGGCTACTATAAGGAAATCTAACACAAACAGCAACTGTTTTTTGTTGTTTACTTTTGCATCTTTACTTGTGGAGCTGTGGCAAGTCCTCATATCAAATACAGAACATGATCTTCCTCCTGCTAATGTTGAGCCTGGAATTGCAGCTTCACCAGATAGCAGCTTTATTCACAGTGACAGTCCCTAAGGAACTGTACATAATAGAGCATGGCAGCAATGTGACCCTGGAATGCAACTTTGACACTGGAAGTCATGTGAACCTTGGAGCAATAACAGCCAGTTTGCAAAAGGTGGAAAATGATACATCCCCACACCGTGAAAGAGCCACTTTGCTGGAGGAGCAGCTGCCCCTAGGGAAGGCCTCGTTCCACATACCTCAAGTCCAAGTGAGGGACGAAGGACAGTACCAATGCATAATCATCTATGGGGTCGCCTGGGACTACAAGTACCTGACTCTGAAAGTCAAAGCTTCCTACAGGAAAATAAACACTCACATCCTAAAGGTTCCAGAAACAGATGAGGTAGAGCTCACCTGCCAGGCTACAGGTTATCCTCTGGCAGAAGTATCCTGGCCAAACGTCAGCGTTCCTGCCAACACCAGCCACTCCAGGACCCCTGAAGGCCTCTACCAGGTCACCAGTGTTCTGCGCCTAAAGCCACCCCCTGGCAGAAACTTCAGCTGTGTGTTCTGGAATACTCACGTGAGGGAACTTACTTTGGCCAGCATTGACCTTCAAAGTCAGATGGAACCCAGGACCCATCCAACTTGGCTGCTTCACATTTTCATCCCCTTCTGCATCATTGCTTTCATTTTCATAGCCACAGTGATAGCCCTAAGAAAACAACTCTGTCAAAAGCTGTATTCTTCAAAAGACACAACAAAAAGACCTGTCACCACAACAAAGAGGGAAGTGAACAGTGCTATCTGAACCTGTGGTCTTGGGAGCCAGGGTGACCTGATATGACATCTAAAGAAGCTTCTGGACTCTGAACAAGAATTCGGTGGCCTGCAGAGCTTGCCATTTGCACTTTTCAAATGCCTTTGGATGACCCAGCACTTTAATCTGAAACCTGCAACAAGACTAGCCAACACCTGGCCATGAAACTTGCCCCTTCACTGATCTGGACTCACCTCTGGAGCCTATGGCTTTAAGCAAGCACTACTGCACTTTACAGAATTACCCCACTGGATCCTGGACCCACAGAATTCCTTCAGGATCCTTCTTGCTGCCAGACTGAAAGCAAAAGGAATTATTTCCCCTCAAGTTTTCTAAGTGATTTCCAAAAGCAGAGGTGTGTGGAAATTTCCAGTAACAGAAACAGATGGGTTGCCAATAGAGTTATTTTTTATCTATAGCTTCCTCTGGGTACTAGAAGAGGCTATTGAGACTATGAGCTCACAGACAGGGCTTCGCACAAACTCAAATCATAATTGACATGTTTTATGGATTACTGGAATCTTGATAGCATAATGAAGTTGTTCTAATTAACAGAGAGCATTTAAATATACACTAAGTGCACAAATTGTGGAGTAAAGTCATCAAGCTCTGTTTTTGAGGTCTAAGTCACAAAGCATTTGTTTTAACCTGTAATGGCACCATGTTTAATGGTGGTTTTTTTTTTGAACTACATCTTTCCTTTAAAAATTATTGGTTTCTTTTTATTTGTTTTTACCTTAGAAATCAATTATATACAGTCAAAAATATTTGATATGCTCATACGTTGTATCTGCAGCAATTTCAGATAAGTAGCTAAAATGGCCAAAGCCCCAAACTAAGCCTCCTTTTCTGGCCCTCAATATGACTTTAAATTTGACTTTTCAGTGCCTCAGTTTGCACATCTGTAATACAGCAATGCTAAGTAGTCAAGGCCTTTGATAATTGGCACTATGGAAATCCTGCAAGATCCCACTACATATGTGTGGAGCAGAAGGGTAACTCGGCTACAGTAACAGCTTAATTTTGTTAAATTTGTTCTTTATACTGGAGCCATGAAGCTCAGAGCATTAGCTGACCCTTGAACTATTCAAATGGGCACATTAGCTAGTATAACAGACTTACATAGGTGGGCCTAAAGCAAGCTCCTTAACTGAGCAAAATTTGGGGCTTATGAGAATGAAAGGGTGTGAAATTGACTAACAGACAAATCATACATCTCAGTTTCTCAATTCTCATGTAAATCAGAGAATGCCTTTAAAGAATAAAACTCAATTGTTATTCTTCAACGTTCTTTATATATTCTACTTTTGGGTA (SEQ ID NO: 5) >NP_079515.2 programmed cell death 1 ligand 2 precursor[Homo sapiens] MIFLLLMLSLELQLHQIAALFTVTVPKELYIIEHGSNVTLECNFDTGSHVNLGAITASLQKVENDTSPHRERATLLEEQLPLGKASFHIPQVQVRDEGQYQCIIIYGVAWDYKYLTLKVKASYRKINTHILKVPETDEVELTCQATGYPLAEVSWPNVSVPANTSHSRTPEGLYQVTSVLRLKPPPGRNFSCVFWNTHVRELTLASIDLQSQMEPRTHPTWLLHIFIPFCIIAFIFIATVIALRKQLCQKLYSSKDTTKRPVTTTKREVNSAI (SEQ ID NO: 6) Mouse PD-L2>NM_021396.2 Mus musculus programmed cell death 1 ligand2 (Pdcd1lg2), mRNAGACCACATCATTTTTGTTCCCTTTGTTGGATATATCCTAATGTCAAATGTGGCATATCTTTGTTGTCTCCTTCTGTCTCCCAACTAGAGAGAACACACTTACGGCTCCTGTCCCGGGCAGGTTTGGTTGTCGGTGTGATTGGCTTCCAGGGAACCTGATACAAGGAGCAACTGTGTGCTGCCTTTTCTGTGTCTTTGCTTGAGGAGCTGTGCTGGGTGCTGATATTGACACAGACCATGCTGCTCCTGCTGCCGATACTGAACCTGAGCTTACAACTTCATCCTGTAGCAGCTTTATTCACCGTGACAGCCCCTAAAGAAGTGTACACCGTAGACGTCGGCAGCAGTGTGAGCCTGGAGTGCGATTTTGACCGCAGAGAATGCACTGAACTGGAAGGGATAAGAGCCAGTTTGCAGAAGGTAGAAAATGATACGTCTCTGCAAAGTGAAAGAGCCACCCTGCTGGAGGAGCAGCTGCCCCTGGGAAAGGCTTTGTTCCACATCCCTAGTGTCCAAGTGAGAGATTCCGGGCAGTACCGTTGCCTGGTCATCTGCGGGGCCGCCTGGGACTACAAGTACCTGACGGTGAAAGTCAAAGCTTCTTACATGAGGATAGACACTAGGATCCTGGAGGTTCCAGGTACAGGGGAGGTGCAGCTTACCTGCCAGGCTAGAGGTTATCCCCTAGCAGAAGTGTCCTGGCAAAATGTCAGTGTTCCTGCCAACACCAGCCACATCAGGACCCCCGAAGGCCTCTACCAGGTCACCAGTGTTCTGCGCCTCAAGCCTCAGCCTAGCAGAAACTTCAGCTGCATGTTCTGGAATGCTCACATGAAGGAGCTGACTTCAGCCATCATTGACCCTCTGAGTCGGATGGAACCCAAAGTCCCCAGAACGTGGCCACTTCATGTTTTCATCCCGGCCTGCACCATCGCTTTGATCTTCCTGGCCATAGTGATAATCCAGAGAAAGAGGATCTAGGGGAAGCTGTATTACGGAAGAAGATCTGGACCTGCGGTCTTGGGAGTTGGAAGGATCTGATGGGAAACCCTCAAGAGACTTCTGGACTCAAAGTGAGAATCTTGCAGGACCTGCCATTTGCACTTTTGAACCCTTTGGACGGTGACCCAGGGCTCCGAAGAGGAGCTTGTAAGACTGACAATCTTCCCTCTGTCTCAAGACTCTCTGAACAGCAAGACCCCAATGGCACTTTAGACTTACCCCTGGGATCCTGGACCCCAGTGAGGGCCTAAGGCTCCTAATGACTTTCAGGGTGAGAACAAAAGGAATTGCTCTCCGCCCCACCCCCACCTCCTGCTTTCCGCAGGGAGACATGGAAATTCCCAGTTACTAAAATAGATTGTCAATAGAGTTATTTATAGCCCTCATTTCCTCCGGGGACTTGGAAGCTTCAGACAGGGTTTTTCATAAACAAAGTCATAACTGATGTGTTTTACAGCATCCTAGAATCCTGGCAGCCTCTGAAGTTCTAATTAACTGGAAGCATTTAAGCAACACGTTAAGTACCCCCACTGTGGTATTTGTTTCTACTTTTCTGTTTTTAAAGTGTGAGTCACAAGGTAATTGTTGTAACCTGTGATATCACTGTTTCTTGTGTCTCTTCTTTCAACTACATCTTTTAAAACAAAACGGTGTGGGGTTTGGTTGTTTTGGTGGTAGTGGTAGTGTTTCTCAGTGGTATCTCCTTAAGAAAAAAAATCATCATGCCAGTGAATTGTTTCTTCAGCCATTTCAGATGGGAAGCTGGAATAGCCTGTCCCCCAAGCTAAGCCTTCTTCCCTAGCTTTCTGCGTGATTTTACATTGAGCATTCCTGTTGCTTTGTTTCTATAACTGTAATGTGGTGATGTCATTGTTAGGGCACTTGAGGGTGGGCGTTCTGGAAGTCCTTTCAGGTTAGTGTTTGGGGGCAGGGTTGCTCAGAATACATAAAGGTGCTAACTTAAACTGCAGCCATGGAGCTCAGTGAATTCACTAACCTTCGGGCTGTCCAAATGTGCACATTAGCTACTGTGACCCCTGTAGGTTAGGGAGCCTGAAGCCAGCTCTTTACCTGGTGTTTAGACTCAGCAGAATTTGGAGTCAATGGGACCAAATGGTTGTGAAATTAAGATTTGAAGTGTGCATCTTATTTTATCACCATCTGCCCAACAAAACTTCAGAAAATGCCTTTGAAGCACAAAAATGTAATCGTTTATGTGAAATCTCTGAGTTGCATTTAGATGCCCATTGCAGCAAGGTGGCTCTCTCACAGATTCCACACCTTAGCCTAAGATACCAGACAGCAGGACAGAGAGAAAAGTCCTTCCTGGTGTGCAAACTTCCTTACACTGGACCTCGCCTCTCAGGTGTGTGATTGGTAGGCCAAATCCCGATAGCCAATCGGTGTTGGGTGCTTTGTCTGCTCTACTGGGAGTCCAGTGGTACAATGGATTCTGGCAAAATGCTGCCATCTTGGCCCTCGCTGGGCTGCTTTCTAGGATATTCATAGAGAAAGGGCCGTCCAGATCCAGTATCCTAAAATCCTGAGAGGAGAATATAAGTTAGTGTGTCTCACTATAACTATCTCTATGATCGGTCACATTACTATCTAACAGTTACCAAATACTATATGCCTAATACTGGTAAGCATTTTATACACACCATTGGATTGAATCCTCTCAAAATCCTCAAAAAGGAAGTTATTAATACCTCCATAGGCAAGGAGCCCAGAACCCAGAGAGGTCAGGCAGTCTAGTTATAGATGCCTGCTTTGTTTAGAAGTGAACAAGAGCATCAAATTATTAATGTGCCCTGGTTATTAATGCGCCCTGGTTACCTGCTGGATGGAACATCAAGGTGGACTTTTGGCAGTTGCATACACCCAGAGGTATTTTGGCTATTCACGGATTAATTTCACACGAAGTGTTTCAGAGACATGTGTAGGGGAAGTCCGGGTTCAGGGGGCCTAAGATTCAAACTCTAGCTTAGCTACGTCTGACCTCCCTAAGCACTAACTTACTATCAAAAGAATGAGCAGTAAAAGAATGGTGTTTACTGCCTGCCTTTATCAGGCAGTGAACGTGCAGCGGGCAACGAATGCTTGATAAGTGTGTGTCAGTGTGAAGTCCCATGTACCAGCCGCTGTCCCCACTGCAAAAGCAGCAGAGCGCTCAGACATCATCAGCTGATTTACCAGCAGCAGATTTCTTCTTCTAGTCCCATCCCTGAAGAAGCTTCCAGCCTAGGTACATTGCATGGGCTTTGTGCTCCAGGAGTTCCTACACAGCCCTCAACTTCAACACAGGCAAAGTGCTTACTGATCCTCATGTATCTTACAGGGTCCCCTCTACCCACAATACCTCATTGCTGGAACTTCAAATCTTCCTGAATAAAAGCTTGCCCGTGGTTTAATTA (SEQID NO: 7) >NP_067371.1 programmed cell death 1 ligand 2 precursor[Mus musculus] MLLLLPILNLSLQLHPVAALFTVTAPKEVYTVDVGSSVSLECDFDRRECTELEGIRASLQKVENDTSLQSERATLLEEQLPLGKALFHIPSVQVRDSGQYRCLVICGAAWDYKYLTVKVKASYMRIDTRILEVPGTGEVQLTCQARGYPLAEVSWQNVSVPANTSHIRTPEGLYQVTSVLRLKPQPSRNFSCMFWNAHMKELTSAIIDPLSRMEPKVPRTWPLHVFIPACTIALIFLAIVIIQRKRI (SEQ ID NO: 8) Human>NM_005214.5 Homo sapiens cytotoxic T-lymphocyte CTLA-4associated protein 4 (CTLA4), transcript variant 1, mRNA (CD152)GCTTTCTATTCAAGTGCCTTCTGTGTGTGCACATGTGTAATACATATCTGGGATCAAAGCTATCTATATAAAGTCCTTGATTCTGTGTGGGTTCAAACACATTTCAAAGCTTCAGGATCCTGAAAGGTTTTGCTCTACTTCCTGAAGACCTGAACACCGCTCCCATAAAGCCATGGCTTGCCTTGGATTTCAGCGGCACAAGGCTCAGCTGAACCTGGCTACCAGGACCTGGCCCTGCACTCTCCTGTTTTTTCTTCTCTTCATCCCTGTCTTCTGCAAAGCAATGCACGTGGCCCAGCCTGCTGTGGTACTGGCCAGCAGCCGAGGCATCGCCAGCTTTGTGTGTGAGTATGCATCTCCAGGCAAAGCCACTGAGGTCCGGGTGACAGTGCTTCGGCAGGCTGACAGCCAGGTGACTGAAGTCTGTGCGGCAACCTACATGATGGGGAATGAGTTGACCTTCCTAGATGATTCCATCTGCACGGGCACCTCCAGTGGAAATCAAGTGAACCTCACTATCCAAGGACTGAGGGCCATGGACACGGGACTCTACATCTGCAAGGTGGAGCTCATGTACCCACCGCCATACTACCTGGGCATAGGCAACGGAACCCAGATTTATGTAATTGATCCAGAACCGTGCCCAGATTCTGACTTCCTCCTCTGGATCCTTGCAGCAGTTAGTTCGGGGTTGTTTTTTTATAGCTTTCTCCTCACAGCTGTTTCTTTGAGCAAAATGCTAAAGAAAAGAAGCCCTCTTACAACAGGGGTCTATGTGAAAATGCCCCCAACAGAGCCAGAATGTGAAAAGCAATTTCAGCCTTATTTTATTCCCATCAATTGAGAAACCATTATGAAGAAGAGAGTCCATATTTCAATTTCCAAGAGCTGAGGCAATTCTAACTTTTTTGCTATCCAGCTATTTTTATTTGTTTGTGCATTTGGGGGGAATTCATCTCTCTTTAATATAAAGTTGGATGCGGAACCCAAATTACGTGTACTACAATTTAAAGCAAAGGAGTAGAAAGACAGAGCTGGGATGTTTCTGTCACATCAGCTCCACTTTCAGTGAAAGCATCACTTGGGATTAATATGGGGATGCAGCATTATGATGTGGGTCAAGGAATTAAGTTAGGGAATGGCACAGCCCAAAGAAGGAAAAGGCAGGGAGCGAGGGAGAAGACTATATTGTACACACCTTATATTTACGTATGAGACGTTTATAGCCGAAATGATCTTTTCAAGTTAAATTTTATGCCTTTTATTTCTTAAACAAATGTATGATTACATCAAGGCTTCAAAAATACTCACATGGCTATGTTTTAGCCAGTGATGCTAAAGGTTGTATTGCATATATACATATATATATATATATATATATATATATATATATATATATATATATATATATATATTTTAATTTGATAGTATTGTGCATAGAGCCACGTATGTTTTTGTGTATTTGTTAATGGTTTGAATATAAACACTATATGGCAGTGTCTTTCCACCTTGGGTCCCAGGGAAGTTTTGTGGAGGAGCTCAGGACACTAATACACCAGGTAGAACACAAGGTCATTTGCTAACTAGCTTGGAAACTGGATGAGGTCATAGCAGTGCTTGATTGCGTGGAATTGTGCTGAGTTGGTGTTGACATGTGCTTTGGGGCTTTTACACCAGTTCCTTTCAATGGTTTGCAAGGAAGCCACAGCTGGTGGTATCTGAGTTGACTTGACAGAACACTGTCTTGAAGACAATGGCTTACTCCAGGAGACCCACAGGTATGACCTTCTAGGAAGCTCCAGTTCGATGGGCCCAATTCTTACAAACATGTGGTTAATGCCATGGACAGAAGAAGGCAGCAGGTGGCAGAATGGGGTGCATGAAGGTTTCTGAAAATTAACACTGCTTGTGTTTTTAACTCAATATTTTCCATGAAAATGCAACAACATGTATAATATTTTTAATTAAATAAAAATCTGTGGTGGTCGTTTTCCGGA (SEQ ID NO: 9) >NP_005205.2 cytotoxic T-lymphocyte protein 4 isoformCTLA4-TM precursor [Homo sapiens]MACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDFLLWILAAVSSGLFFYSFLLTAVSLSKMLKKRSPLTTGVYVKMPPTEPECEKQFQPYFIPIN (SEQ ID NO: 10)Mouse CTLA- >NM_009843.4 Mus musculus cytotoxic T-lymphocyte- 4 (CD152)associated protein 4 (Ctla4), transcript variant 1, mRNACTACACATATGTAGCACGTACCTTGGATCAAAGCTGTCTATATAAAGTCCCCGAGTCTGTGTGGGTTCAAACACATCTCAAGGCTTCTGGATCCTGTTGGGTTTTACTCTGCTCCCTGAGGACCTCAGCACATTTGCCCCCCAGCCATGGCTTGTCTTGGACTCCGGAGGTACAAAGCTCAACTGCAGCTGCCTTCTAGGACTTGGCCTTTTGTAGCCCTGCTCACTCTTCTTTTCATCCCAGTCTTCTCTGAAGCCATACAGGTGACCCAACCTTCAGTGGTGTTGGCTAGCAGCCATGGTGTCGCCAGCTTTCCATGTGAATATTCACCATCACACAACACTGATGAGGTCCGGGTGACTGTGCTGCGGCAGACAAATGACCAAATGACTGAGGTCTGTGCCACGACATTCACAGAGAAGAATACAGTGGGCTTCCTAGATTACCCCTTCTGCAGTGGTACCTTTAATGAAAGCAGAGTGAACCTCACCATCCAAGGACTGAGAGCTGTTGACACGGGACTGTACCTCTGCAAGGTGGAACTCATGTACCCACCGCCATACTTTGTGGGCATGGGCAACGGGACGCAGATTTATGTCATTGATCCAGAACCATGCCCGGATTCTGACTTCCTCCTTTGGATCCTTGTCGCAGTTAGCTTGGGGTTGTTTTTTTACAGTTTCCTGGTCACTGCTGTTTCTTTGAGCAAGATGCTAAAGAAAAGAAGTCCTCTTACAACAGGGGTCTATGTGAAAATGCCCCCAACAGAGCCAGAATGTGAAAAGCAATTTCAGCCTTATTTTATTCCCATCAACTGAAAGGCCGTTTATGAAGAAGAAGGAGCATACTTCAGTCTCTAAAAGCTGAGGCAATTTCAACTTTCCTTTTCTCTCCAGCTATTTTTACCTGTTTGTATATTTTAAGGAGAGTATGCCTCTCTTTAATAGAAAGCTGGATGCAAAATTCCAATTAAGCATACTACAATTTAAAGCTAAGGAGCATGAACAGAGAGCTGGGATATTTCTGTTGTGTCAGAACCATTTTACTAAAAGCATCACTTGGAAGCAGCATAAGGATATAGCATTATGGTGTGGGGTCAAGGGAACATTAGGGAATGGCACAGCCCAAAGAAAGGAAGGGGGTGAAGGAAGAGATTATATTGTACACATCTTGTATTTACCTGAGAGATGTTTATGACTTAAATAATTTTTAAATTTTTCATGCTGTTATTTTCTTTAACAATGTATAATTACACGAAGGTTTAAACATTTATTCACAGAGCTATGTGACATAGCCAGTGGTTCCAAAGGTTGTAGTGTTCCAAGATGTATTTTTAAGTAATATTGTACATGGGTGTTTCATGTGCTGTTGTGTATTTGCTGGTGGTTTGAATATAAACACTATGTATCAGTGTCGTCCCACAGTGGGTCCTGGGGAGGTTTGGCTGGGGAGCTTAGGACACTAATCCATCAGGTTGGACTCGAGGTCCTGCACCAACTGGCTTGGAAACTAGATGAGGCTGTCACAGGGCTCAGTTGCATAAACCGATGGTGATGGAGTGTAAACTGGGTCTTTACACTCATTTTATTTTTTGTTTCTGCTTTTGTTTTCTTCAATGATTTGCAAGGAAACCAAAAGCTGGCAGTGTTTGTATGAACCTGACAGAACACTGTCTTCAAGGAAATGCCTCATTCCTGAGACCAGTAGGTTTGTTTTTTTAGGAAGTTCCAATACTAGGACCCCCTACAAGTACTATGGCTCCTCGAAAACACAAAGTTAATGCCACAGGAAGCAGCAGATGGTAGGATGGGATGCACAAGAGTTCCTGAAAACTAACACTGTTAGTGTTTTTTTTTTAACTCAATATTTTCCATGAAAATGCAACCACATGTATAATATTTTTAATTAAATAAAAGTTTCTTGTGATTGTTTT (SEQID NO: 11) >NP_033973.2 cytotoxic T-lymphocyte protein 4 isoform 1precursor [Mus musculus]MACLGLRRYKAQLQLPSRTWPFVALLTLLFIPVFSEAIQVTQPSVVLASSHGVASFPCEYSPSHNTDEVRVTVLRQTNDQMTEVCATTFTEKNTVGFLDYPFCSGTFNESRVNLTIQGLRAVDTGLYLCKVELMYPPPYFVGMGNGTQIYVIDPEPCPDSDFLLWILVAVSLGLFFYSFLVTAVSLSKMLKKRSPLTTGVYVKMPPTEPECEKQFQPYFIPIN (SEQ ID NO: 12)Human 4- >NM_003811.4 Homo sapiens TNF superfamily member 9 1BBL(TNFSF9), mRNA (CD137L)AGTCTCTCGTCATGGAATACGCCTCTGACGCTTCACTGGACCCCGAAGCCCCGTGGCCTCCCGCGCCCCGCGCTCGCGCCTGCCGCGTACTGCCTTGGGCCCTGGTCGCGGGGCTGCTGCTGCTGCTGCTGCTCGCTGCCGCCTGCGCCGTCTTCCTCGCCTGCCCCTGGGCCGTGTCCGGGGCTCGCGCCTCGCCCGGCTCCGCGGCCAGCCCGAGACTCCGCGAGGGTCCCGAGCTTTCGCCCGACGATCCCGCCGGCCTCTTGGACCTGCGGCAGGGCATGTTTGCGCAGCTGGTGGCCCAAAATGTTCTGCTGATCGATGGGCCCCTGAGCTGGTACAGTGACCCAGGCCTGGCAGGCGTGTCCCTGACGGGGGGCCTGAGCTACAAAGAGGACACGAAGGAGCTGGTGGTGGCCAAGGCTGGAGTCTACTATGTCTTCTTTCAACTAGAGCTGCGGCGCGTGGTGGCCGGCGAGGGCTCAGGCTCCGTTTCACTTGCGCTGCACCTGCAGCCACTGCGCTCTGCTGCTGGGGCCGCCGCCCTGGCTTTGACCGTGGACCTGCCACCCGCCTCCTCCGAGGCTCGGAACTCGGCCTTCGGTTTCCAGGGCCGCTTGCTGCACCTGAGTGCCGGCCAGCGCCTGGGCGTCCATCTTCACACTGAGGCCAGGGCACGCCATGCCTGGCAGCTTACCCAGGGCGCCACAGTCTTGGGACTCTTCCGGGTGACCCCCGAAATCCCAGCCGGACTCCCTTCACCGAGGTCGGAATAACGTCCAGCCTGGGTGCAGCCCACCTGGACAGAGTCCGAATCCTACTCCATCCTTCATGGAGACCCCTGGTGCTGGGTCCCTGCTGCTTTCTCTACCTCAAGGGGCTTGGCAGGGGTCCCTGCTGCTGACCTCCCCTTGAGGACCCTCCTCACCCACTCCTTCCCCAAGTTGGACCTTGATATTTATTCTGAGCCTGAGCTCAGATAATATATTATATATATTATATATATATATATATTTCTATTTAAAGAGGATCCTGAGTTTGTGAATGGACTTTTTTAGAGGAGTTGTTTTGGGGGGGGGGGGGTCTTCGACATTGCCGAGGCTGGTCTTGAACTCCTGGACTTAGACGATCCTCCTGCCTCAGCCTCCCAAGCAACTGGGATTCATCCTTTCTATTAATTCATTGTACTTATTTGCTTATTTGTGTGTATTGAGCATCTGTAATGTGCCAGCATTGTGCCCAGGCTAGGGGGCTATAGAAACATCTAGAAATAGACTGAAAGAAAATCTGAGTTATGGTAATACGTGAGGAATTTAAAGACTCATCCCCAGCCTCCACCTCCTGTGTGATACTTGGGGGCTAGCTTTTTTCTTTCTTTCTTTTTTTTGAGATGGTCTTGTTCTGTCAACCAGGCTAGAATGCAGCGGTGCAATCATGAGTCAATGCAGCCTCCAGCCTCGACCTCCCGAGGCTCAGGTGATCCTCCCATCTCAGCCTCTCGAGTAGCTGGGACCACAGTTGTGTGCCACCACACTTGGCTAACTTTTTAATTTTTTTGCGGAGACGGTATTGCTATGTTGCCAAGGTTGTTTACATGCCAGTACAATTTATAATAAACACTCATTTTTCCTCCC (SEQ ID NO: 13) >NP_003802.1 tumor necrosis factor ligand superfamilymember 9 [Homo sapiens]MEYASDASLDPEAPWPPAPRARACRVLPWALVAGLLLLLLLAAACAVFLACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSPRSE (SEQ ID NO: 14) Mouse 4-1BBL >NM_009404.3 Mus musculus tumor necrosis factor (ligand) (CD137L)superfamily, member 9 (Tnfsf9), mRNAATAAAGCACGGGCACTGGCGGGAGACGTGCACTGACCGACCGTGGTAATGGACCAGCACACACTTGATGTGGAGGATACCGCGGATGCCAGACATCCAGCAGGTACTTCGTGCCCCTCGGATGCGGCGCTCCTCAGAGATACCGGGCTCCTCGCGGACGCTGCGCTCCTCTCAGATACTGTGCGCCCCACAAATGCCGCGCTCCCCACGGATGCTGCCTACCCTGCGGTTAATGTTCGGGATCGCGAGGCCGCGTGGCCGCCTGCACTGAACTTCTGTTCCCGCCACCCAAAGCTCTATGGCCTAGTCGCTTTGGTTTTGCTGCTTCTGATCGCCGCCTGTGTTCCTATCTTCACCCGCACCGAGCCTCGGCCAGCGCTCACAATCACCACCTCGCCCAACCTGGGTACCCGAGAGAATAATGCAGACCAGGTCACCCCTGTTTCCCACATTGGCTGCCCCAACACTACACAACAGGGCTCTCCTGTGTTCGCCAAGCTACTGGCTAAAAACCAAGCATCGTTGTGCAATACAACTCTGAACTGGCACAGCCAAGATGGAGCTGGGAGCTCATACCTATCTCAAGGTCTGAGGTACGAAGAAGACAAAAAGGAGTTGGTGGTAGACAGTCCCGGGCTCTACTACGTATTTTTGGAACTGAAGCTCAGTCCAACATTCACAAACACAGGCCACAAGGTGCAGGGCTGGGTCTCTCTTGTTTTGCAAGCAAAGCCTCAGGTAGATGACTTTGACAACTTGGCCCTGACAGTGGAACTGTTCCCTTGCTCCATGGAGAACAAGTTAGTGGACCGTTCCTGGAGTCAACTGTTGCTCCTGAAGGCTGGCCACCGCCTCAGTGTGGGTCTGAGGGCTTATCTGCATGGAGCCCAGGATGCATACAGAGACTGGGAGCTGTCTTATCCCAACACCACCAGCTTTGGACTCTTTCTTGTGAAACCCGACAACCCATGGGAATGAGAACTATCCTTCTTGTGACTCCTAGTTGCTAAGTCCTCAAGCTGCTATGTTTTATGGGGTCTGAGCAGGGGTCCCTTCCATGACTTTCTCTTGTCTTTAACTGGACTTGGTATTTATTCTGAGCATAGCTCAGACAAGACTTTATATAATTCACTAGATAGCATTAGTAAACTGCTGGGCAGCTGCTAGATAAAAAAAAATTTCTAAATCAAAGTTTATATTTATATTAATATATAAAAATAAATGTGTTTGT (SEQ ID NO: 15) >NP_033430.1 tumor necrosis factor ligand superfamilymember 9 [Mus musculus]MDQHTLDVEDTADARHPAGTSCPSDAALLRDTGLLADAALLSDTVRPTNAALPTDAAYPAVNVRDREAAWPPALNFCSRHPKLYGLVALVLLLLIAACVPIFTRTEPRPALTITTSPNLGTRENNADQVTPVSHIGCPNTTQQGSPVFAKLLAKNQASLCNTTLNWHSQDGAGSSYLSQGLRYEEDKKELVVDSPGLYYVFLELKLSPTFTNTGHKVQGWVSLVLQAKPQVDDFDNLALTVELFPCSMENKLVDRSWSQLLLLKAGHRLSVGLRAYLHGAQDAYRDWELSYPNTTSFGLFLVKPDNPWE (SEQ ID NO: 16) Human>NM_003820.4 Homo sapiens TNF receptor superfamily member HVEM14 (TNFRSF14), transcript variant 1, DNA (CD270)ATACCGGCCCTTCCCCTCGGCTTTGCCTGGACAGCTCCTGCCTCCCGCAGGGCCCACCTGTGTCCCCCAGCGCCGCTCCACCCAGCAGGCCTGAGCCCCTCTCTGCTGCCAGACACCCCCTGCTGCCCACTCTCCTGCTGCTCGGGTTCTGAGGCACAGCTTGTCACACCGAGGCGGATTCTCTTTCTCTTTCTCTTTCTCTTCTGGCCCACAGCCGCAGCAATGGCGCTGAGTTCCTCTGCTGGAGTTCATCCTGCTAGCTGGGTTCCCGAGCTGCCGGTCTGAGCCTGAGGCATGGAGCCTCCTGGAGACTGGGGGCCTCCTCCCTGGAGATCCACCCCCAAAACCGACGTCTTGAGGCTGGTGCTGTATCTCACCTTCCTGGGAGCCCCCTGCTACGCCCCAGCTCTGCCGTCCTGCAAGGAGGACGAGTACCCAGTGGGCTCCGAGTGCTGCCCCAAGTGCAGTCCAGGTTATCGTGTGAAGGAGGCCTGCGGGGAGCTGACGGGCACAGTGTGTGAACCCTGCCCTCCAGGCACCTACATTGCCCACCTCAATGGCCTAAGCAAGTGTCTGCAGTGCCAAATGTGTGACCCAGCCATGGGCCTGCGCGCGAGCCGGAACTGCTCCAGGACAGAGAACGCCGTGTGTGGCTGCAGCCCAGGCCACTTCTGCATCGTCCAGGACGGGGACCACTGCGCCGCGTGCCGCGCTTACGCCACCTCCAGCCCGGGCCAGAGGGTGCAGAAGGGAGGCACCGAGAGTCAGGACACCCTGTGTCAGAACTGCCCCCCGGGGACCTTCTCTCCCAATGGGACCCTGGAGGAATGTCAGCACCAGACCAAGTGCAGCTGGCTGGTGACGAAGGCCGGAGCTGGGACCAGCAGCTCCCACTGGGTATGGTGGTTTCTCTCAGGGAGCCTCGTCATCGTCATTGTTTGCTCCACAGTTGGCCTAATCATATGTGTGAAAAGAAGAAAGCCAAGGGGTGATGTAGTCAAGGTGATCGTCTCCGTCCAGCGGAAAAGACAGGAGGCAGAAGGTGAGGCCACAGTCATTGAGGCCCTGCAGGCCCCTCCGGACGTCACCACGGTGGCCGTGGAGGAGACAATACCCTCATTCACGGGGAGGAGCCCAAACCACTGACCCACAGACTCTGCACCCCGACGCCAGAGATACCTGGAGCGACGGCTGCTGAAAGAGGCTGTCCACCTGGCGGAACCACCGGAGCCCGGAGGCTTGGGGGCTCCGCCCTGGGCTGGCTTCCGTCTCCTCCAGTGGAGGGAGAGGTGGGGCCCCTGCTGGGGTAGAGCTGGGGACGCCACGTGCCATTCCCATGGGCCAGTGAGGGCCTGGGGCCTCTGTTCTGCTGTGGCCTGAGCTCCCCAGAGTCCTGAGGAGGAGCGCCAGTTGCCCCTCGCTCACAGACCACACACCCAGCCCTCCTGGGCCAGCCCAGAGGGCCCTTCAGACCCCAGCTGTCTGCGCGTCTGACTCTTGTGGCCTCAGCAGGACAGGCCCCGGGCACTGCCTCACAGCCAAGGCTGGACTGGGTTGGCTGCAGTGTGGTGTTTAGTGGATACCACATCGGAAGTGATTTTCTAAATTGGATTTGAATTCGGCTCCTGTTTTCTATTTGTCATGAAACAGTGTATTTGGGGAGATGCTGTGGGAGGATGTAAATATCTTGTTTCTCCTCAAA (SEQ IDNO: 17) >NP_003811.2 tumor necrosis factor receptor superfamilymember 14 isoform 1 precursor [Homo sapiens]MEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKEDEYPVGSECCPKCSPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCDPAMGLRASRNCSRTENAVCGCSPGHFCIVQDGDHCAACRAYATSSPGQRVQKGGTESQDTLCQNCPPGTFSPNGTLEECQHQTKCSWLVTKAGAGTSSSHWVWWFLSGSLVIVIVCSTVGLIICVKRRKPRGDVVKVIVSVQRKRQEAEGEATVIEALQAPPDVTTVAVEETIPSFTGRSPNH (SEQ ID NO: 18)Mouse HVEM >NM_178931.2 Mus musculus tumor necrosis factor receptor(CD270) superfamily, member 14 (herpesvirus entry mediator)(Tnfrsf14), mRNAGCTCTTGGCCTGAAGTTTCTTGATCAAGAAAATGGAACCTCTCCCAGGATGGGGGTCGGCACCCTGGAGCCAGGCCCCTACAGACAACACCTTCAGGCTGGTGCCTTGTGTCTTCCTTTTGAACTTGCTGCAGCGCATCTCTGCCCAGCCCTCATGCAGACAGGAGGAGTTCCTTGTGGGAGACGAGTGCTGCCCCATGTGCAACCCAGGTTACCATGTGAAGCAGGTCTGCAGTGAGCATACAGGCACAGTGTGTGCCCCCTGTCCCCCACAGACATATACCGCCCATGCAAATGGCCTGAGCAAGTGTCTGCCCTGCGGAGTCTGTGATCCAGACATGGGCCTGCTGACCTGGCAGGAGTGCTCCAGCTGGAAGGACACTGTGTGCAGATGCATCCCAGGCTACTTCTGTGAGAACCAGGATGGGAGCCACTGTTCCACATGCTTGCAGCACACCACCTGCCCTCCAGGGCAGAGGGTAGAGAAGAGAGGGACTCACGACCAGGACACTGTATGTGCTGACTGCCTAACAGGGACCTTCTCACTTGGAGGGACTCAGGAGGAATGCCTGCCCTGGACCAACTGCAGTGCATTTCAACAGGAAGTAAGACGTGGGACCAACAGCACAGACACCACCTGCTCCTCCCAGGTCGTCTACTACGTTGTGTCCATCCTTTTGCCACTTGTGATAGTGGGAGCTGGGATAGCTGGATTCCTCATCTGCACGCGAAGACACCTGCACACCAGCTCAGTGGCCAAGGAGCTGGAGCCTTTCCAGGAACAACAGGAGAACACCATCAGGTTTCCAGTCACCGAGGTTGGGTTTGCTGAGACCGAGGAGGAGACAGCCTCCAACTGAACAAATTCTGGGTGACAAGACACCGAGGAGACGT (SEQ ID NO: 19) >N5_849262.1 tumor necrosis factor receptor superfamilymember 14 precursor [Mus musculus]MEPLPGWGSAPWSQAPTDNTFRLVPCVFLLNLLQRISAQPSCRQEEFLVGDECCPMCNPGYHVKQVCSEHTGTVCAPCPPQTYTAHANGLSKCLPCGVCDPDMGLLTWQECSSWKDTVCRCIPGYFCENQDGSHCSTCLQHTTCPPGQRVEKRGTHDQDTVCADCLTGTFSLGGTQEECLPWTNCSAFQQEVRRGTNSTDTTCSSQVVYYVVSILLPLVIVGAGIAGFLICTRRHLHTSSVAKELEPFQEQQENTIRFPVTEVGFAETEEETASN (SEQ ID NO: 20)Human FGL1 >NM_004467.4 Homo sapiens fibrinogen like 1 (FGL1),transcript variant 1, mRNAAATGCAGTTACAGGATCCTGGGAAGCAGAGTGTCTGGATGGAACCTGAGCTGGGTCTCTGACTCACTTCTGACTTTAGTTTTTTCAAGGGGGAACATGGCAAAGGTGTTCAGTTTCATCCTTGTTACCACCGCTCTGACAATGGGCAGGGAAATTTCGGCGCTCGAGGACTGTGCCCAGGAGCAGATGCGGCTCAGAGCCCAGGTGCGCCTGCTTGAGACCCGGGTCAAACAGCAACAGGTCAAGATCAAGCAGCTTTTGCAGGAGAATGAAGTCCAGTTCCTTGATAAAGGAGATGAGAATACTGTCATTGATCTTGGAAGCAAGAGGCAGTATGCAGATTGTTCAGAGATTTTCAATGATGGGTATAAGCTCAGTGGATTTTACAAAATCAAACCTCTCCAGAGCCCAGCAGAATTTTCTGTTTATTGTGACATGTCCGATGGAGGAGGATGGACTGTAATTCAGAGACGATCTGATGGCAGTGAAAACTTTAACAGAGGATGGAAAGACTATGAAAATGGCTTTGGAAATTTTGTCCAAAAACATGGTGAATATTGGCTGGGCAATAAAAATCTTCACTTCTTGACCACTCAAGAAGACTACACTTTAAAAATCGACCTTGCAGATTTTGAAAAAAATAGCCGTTATGCACAATATAAGAATTTCAAAGTTGGAGATGAAAAGAATTTCTACGAGTTGAATATTGGGGAATATTCTGGAACAGCTGGAGATTCCCTTGCGGGGAATTTTCATCCTGAGGTGCAGTGGTGGGCTAGTCACCAAAGAATGAAATTCAGCACGTGGGACAGAGATCATGACAACTATGAAGGGAACTGCGCAGAAGAAGATCAGTCTGGCTGGTGGTTTAACAGGTGTCACTCTGCAAACCTGAATGGTGTATACTACAGCGGCCCCTACACGGCTAAAACAGACAATGGGATTGTCTGGTACACCTGGCATGGGTGGTGGTATTCTCTGAAATCTGTGGTTATGAAAATTAGGCCAAATGATTTTATTCCAAATGTAATTTAATTGCTGCTGTTGGGCTTTCGTTTCTGCAATTCAGCTTTGTTTAAAGTGATTTGAAAAATACTCATTCTGAACATATCCATGCGCAATCATGATAACTGTTGTGAGTAGTGCTTTTCATTCTTCTCACTTGCCTTTGTTACTTAATGTGCTTTCAGTACAGCAGATATGCAATATTCACCAAATAAATGTAGACTGTGTTAATA (SEQ ID NO: 21)>NP_004458.3 fibrinogen-like protein 1 precursor [Homo sapiens]MAKVFSFILVTTALTMGREISALEDCAQEQMRLRAQVRLLETRVKQQQVKIKQLLQENEVQFLDKGDENTVIDLGSKRQYADCSEIFNDGYKLSGFYKIKPLQSPAEFSVYCDMSDGGGWTVIQRRSDGSENFNRGWKDYENGFGNFVQKHGEYWLGNKNLHFLTTQEDYTLKIDLADFEKNSRYAQYKNFKVGDEKNFYELNIGEYSGTAGDSLAGNFHPEVQWWASHQRMKFSTWDRDHDNYEGNCAEEDQSGWWFNRCHSANLNGVYYSGPYTAKTDNGIVWYTWHGWWYSLKSVVMKIRPNDFIPNVI (SEQ ID NO: 22) Mouse FGL1>NM_145594.2 Mus musculus fibrinogen-like protein 1 (Fgl1), mRNAGTTAGAAGTTCCTGGGAGGCTCTGTGTGGATGGACTGAGCCTAGCTAAGTCCTGATTCATTTTGACTTGAGTTCTCTCAGTGGGAAGAATGGGAAAGATTTACAGCTTCGTCCTGGTCGCCATTGCTCTGATGATGGGAAGGGAAGGTTGGGCCCTCGAGAGTGAGAACTGCTTGCGGGAGCAGGTGAGGCTCAGGGCTCAGGTGCACCAGCTTGAGACCCGGGTCAAACAACAACAGACCATGATTGCACAGCTCTTGCATGAGAAGGAAGTCCAGTTTCTGGATAAAGGATCGGAGAACAGTTTCATTGACCTTGGAGGCAAGAAGCAGTATGCAGATTGTTCAGAGATTTACAATGACGGATTTAAGCAGAGTGGATTTTACAAAATCAAACCTCTTCAGAGCCTGGCAGAATTCTCTGTTTATTGTGACATGTCTGATGGAGGGGGATGGACTGTAATTCAGAGACGATCTGATGGCAGTGAGAACTTTAACAGGGGTTGGAATGACTATGAAAATGGCTTTGGAAACTTTGTCCAAAACAATGGCGAATACTGGCTGGGTAACAAAAACATTAACTTGCTAACTATTCAAGGAGACTACACTTTAAAAATCGACCTGACAGATTTTGAGAAAAACAGCAGCTTCGCACAATACCAAAGTTTTAAAGTTGGTGATAAAAAGTCTTTTTATGAACTAAATATTGGAGAATATTCTGGCACAGCTGGAGATTCCCTGTCAGGAACTTTTCATCCTGAAGTACAGTGGTGGGCTAGTCACCAAAGGATGAAGTTCAGCACGTGGGACAGAGATAACGACAATTACCAAGGAAACTGTGCTGAGGAAGAGCAGTCTGGCTGGTGGTTTAACAGGTGTCACTCTGCAAACCTGAACGGTGTTTACTACCGTGGTTCCTACAGGGCAGAAACGGATAATGGTGTTGTGTGGTACACCTGGCATGGGTGGTGGTATTCCTTGAAATCTGTGGTTATGAAAATTAGGCCAAGTGATTTTATTCCAAATATTATTTAGTTGCCCTCATTGGGATCTCCTTTCTGTAATTCATCTTGGTTTACTTGAAAATAAATATTTGAAAAAGATATAATTCTGAATAACACA (SEQ ID NO: 23)>NP_663569.2 fibrinogen-like protein 1 precursor [Mus musculus]MGKIYSFVLVAIALMMGREGWALESENCLREQVRLRAQVHQLETRVKQQQTMIAQLLHEKEVQFLDKGSENSFIDLGGKKQYADCSEIYNDGFKQSGFYKIKPLQSLAEFSVYCDMSDGGGWTVIQRRSDGSENFNRGWNDYENGFGNFVQNNGEYWLGNKNINLLTIQGDYTLKIDLTDFEKNSSFAQYQSFKVGDKKSFYELNIGEYSGTAGDSLSGTFHPEVQWWASHQRMKFSTWDRDNDNYQGNCAEEEQSGWWFNRCHSANLNGVYYRGSYRAETDNGVVWYTWHGWWYSLKSVVMKIRPSDFIPNII (SEQ ID NO: 24) Human OX-2>NM_005944.7 Homo sapiens CD200 molecule (CD200), (CD200)transcript variant 1, mRNAAGAGCTCCAGGCGCACATCCGCAGTCAGCCACCTCGCGCGCGCCTCCAGGAGCAAGGATGGAGAGGCTGGTGATCAGGATGCCCTTCTCTCATCTGTCTACCTACAGCCTGGTTTGGGTCATGGCAGCAGTGGTGCTGTGCACAGCACAAGTGCAAGTGGTGACCCAGGATGAAAGAGAGCAGCTGTACACACCTGCTTCCTTAAAATGCTCTCTGCAAAATGCCCAGGAAGCCCTCATTGTGACATGGCAGAAAAAGAAAGCTGTAAGCCCAGAAAACATGGTCACCTTCAGCGAGAACCATGGGGTGGTGATCCAGCCTGCCTATAAGGACAAGATAAACATTACCCAGCTGGGACTCCAAAACTCAACCATCACCTTCTGGAATATCACCCTGGAGGATGAAGGGTGTTACATGTGTCTCTTCAATACCTTTGGTTTTGGGAAGATCTCAGGAACGGCCTGCCTCACCGTCTATGTACAGCCCATAGTATCCCTTCACTACAAATTCTCTGAAGACCACCTAAATATCACTTGCTCTGCCACTGCCCGCCCAGCCCCCATGGTCTTCTGGAAGGTCCCTCGGTCAGGGATTGAAAATAGTACAGTGACTCTGTCTCACCCAAATGGGACCACGTCTGTTACCAGCATCCTCCATATCAAAGACCCTAAGAATCAGGTGGGGAAGGAGGTGATCTGCCAGGTGCTGCACCTGGGGACTGTGACCGACTTTAAGCAAACCGTCAACAAAGGCTATTGGTTTTCAGTTCCGCTATTGCTAAGCATTGTTTCCCTGGTAATTCTTCTCGTCCTAATCTCAATCTTACTGTACTGGAAACGTCACCGGAATCAGGACCGAGAGCCCTAAATAAGTCACACAGCACCCTGAAAGTGATTCCCTGGTCTACTTGAATTTGACACAAGAGAAAAGCAGGAGGAAAAGGGGCCATTCTCCAAAGGACCTGAAAGAGCAAAAGAGGTGGGAGCGAAAGCCTTAAGGATCCCACGACTTTTTACTGCCATCTGAGCTACTCAGTGTTTGAATCCCAAGAGGAAGTCAGTTTACCTCTCAGGTCTGTTGTAGGACTTGATTTTGTAAAGCAATGCCATGTTATGTGGTTGAAAGGGCACTGGACTTAGTTAGTATCAGGAGCACTGAGCTCACAGACTGACTTGGGCTCCTACTGGTGGGGACCTCTGTTAGTCACTTTACCTCATCCAAAGTATAAAGGAATTGGACCAAATAATTTACCACATAGCTCTAAAACTTAATTTAAAATGTAATTCCAGAAAAAAAAAGGGAATAAGCAAAGGGGGAAGAATTGAAAGAGAGAGAGAAGAAAGAATACAGAGAGCTTACCTTTTGCCTTTCTGTTGATGTTACATCTCTTCTTCCTATGTTCTTAGGTCTATGAGTCTGTTTCCCCATCATTTGGTATCTAGTCCAGTTCCTGCTTACTGCTTTGCTAATAGCTGGCCTTGCTAGAATCCTTGGTTTCACTGCTGTTCTTCATGTGCTTCTATGAGATTTACTCCAACACAAATAGGACTGAATTTATTGTGAAGTAACATTGGCAATCTTAACTTATTCATTTAACTTATTTTTATAGCTAGATAAATATTGTTAGTCTTAGACAATAGCTCACATTTTTTGAGAAGCATGCCCTCCCTGTCCATTTGTCTTATAACATGACCCAGCCCTATTTTACGTCATTCTAAATTCAGCCTCATATAATGAAAATACATTATGAAAACAGATGTTTAGGAGATTTCCTGTATAGCAGTCAGCCAATTCATATGCTTTGTCTCTGCTGGCTTCTTTTTCCATGCGTTAACTTTTCCCAATAGCAGAGGAGGCAAATATGAGCATACAATCCCTTTGTTCTAAAGATATTGTTCCAGCTAGTGGAATGATGTTGAATCTTTAATAACCATAATTAGTTGCTTTTTCAGTATCTTCTGCTTTGTCTGTGTCTATCCAGTGGCCTAGGAATTAAAGTGTAAGTTGTTTTCGCTGTTAAATTGGATATTTATATATATATATAGCAAGATTTTCATGTGTTATTTAATTCTGTATTGTTTCTTATATTTGTAGTAAAATATTGAACAATTAAAAGTGTTGACTCCAAA (SEQ ID NO: 25) >NP_005935.4 OX-2 membrane glycoprotein isoform aprecursor [Homo sapiens]MERLVIRMPFSHLSTYSLVWVMAAVVLCTAQVQVVTQDEREQLYTPASLKCSLQNAQEALIVTWQKKKAVSPENMVTFSENHGVVIQPAYKDKINITQLGLQNSTITFWNITLEDEGCYMCLFNTFGFGKISGTACLTVYVQPIVSLHYKFSEDHLNITCSATARPAPMVFWKVPRSGIENSTVTLSHPNGTTSVTSILHIKDPKNQVGKEVICQVLHLGTVTDFKQTVNKGYWFSVPLLLSIVSLVILLVLISILLYWKRHRNQDREP (SEQ ID NO: 26) Mouse OX-2>NM_010818.3 Mus musculus CD200 antigen (Cd200), (CD200)transcript variant 1, mRNAGGGCGTGGTTGGTTGGTCGTCTCTTCCTCCACACTAGAGGAGCTGTAGAGTCTGCCTGTGCAGTGGAGGGGGCTCTCTCTACGGCGAATAGTAGTGTCCCTGCTCACAGGTGTTGCGGAGATATCCTCCATCGTGGAAGAGCTCAGACCCCGAGAAGCTGGTGTCTAGCTGCGGCCCAGAGCAAGGATGGGCAGTCTGGTATTCAGGAGACCTTTCTGCCATCTCTCCACCTACAGCCTGATTTGGGGCATGGCAGCAGTAGCGCTGAGCACAGCTCAAGTGGAAGTGGTGACCCAGGATGAAAGAAAGGCGCTGCACACAACTGCATCCTTACGATGTTCTCTAAAAACATCCCAGGAACCCTTGATTGTGACATGGCAGAAAAAGAAAGCCGTGAGCCCAGAAAACATGGTCACCTACAGCAAAACCCATGGGGTTGTAATCCAGCCTGCCTACAAAGACAGGATAAATGTCACAGAGCTGGGACTCTGGAACTCAAGCATCACCTTCTGGAACACAACATTGGAAGATGAGGGCTGCTACATGTGTCTCTTCAACACGTTTGGTTCTCAGAAGGTCTCAGGAACAGCTTGCCTTACCCTCTATGTACAGCCCATAGTACACCTTCACTACAACTATTTTGAAGACCACCTAAACATCACTTGCTCTGCGACTGCCCGTCCAGCCCCTGCCATCTCCTGGAAGGGTACTGGGACAGGAATTGAGAATAGTACCGAGAGTCACTTCCATTCAAATGGGACTACATCTGTCACCAGCATCCTCCGGGTCAAAGACCCCAAAACTCAAGTTGGGAAGGAAGTGATCTGCCAGGTTTTATACCTGGGGAATGTGATTGACTACAAGCAGAGTCTGGACAAAGGATTTTGGTTTTCAGTTCCACTGTTGCTAAGCATTGTTTCTCTGGTAATTCTTCTGATCTTGATCTCCATCTTACTATACTGGAAACGTCACCGAAATCAGGAGCGGGGTGAATCATCACAGGGGATGCAAAGAATGAAATAAGAGCTCTAAAGAAATTATACAGAACCCTGAACGTGTTTCCCTGGTCTACTTGAATCTGATGTGAAAGAAAAGCAGGAGGGAAAAGGCCATTCTCCATAGGACCTAAGGAGAGCAAAAGACCAGACACGAGCCTGTGAGGGATTTGACTTTTTGCTGTTGTCCCAGGTCCTCGGTGTTTGCATTCCAAGAGGAAGTCGAGTGCCTCGGGTCTGTTGTAGGACTTGATTTTTTTTTTTTTTGTAGAGCAATGCAGTGCCATGCTGTTAGAAAGGCTCCAGACTTAGAACCACCAGTGCCAAGCCAGCTCTCAGACCGACTAGGGCTCCCATCGGAGGAACAAATCGTAGTCAACTTACCTCACAGAGCTCTCTGGTCCTTACACAAAGTAGAAAGGAGTGGGACCAGAAAATTGGCCATGTCTGAAATCTGATGGAATTTTTAGGAAGAAAACTGAAGAATAAGCAAAAGAAGAAAGAACACAGAAGGGTCCAAAGAGCTTCTGAGAGTACCTTTTGCCTTTCTGTTGGTGTCCCAGCTCTGGTTTTGTTCTTAGGTCCGCCAGTGTGTTTCCCTGTTGTTTGAGTATCTAGTTGACTACCTGCTACTGTTCTGCTGATGGTTGGCCTTGCTAGAATCCCTGACTCCCCTGCCGTTCTCTATGTGCTTCTATGAGGGTTACTATGATGAAAATAGAGCAGAAGATAGTGTGAAGTAACATTGGCAACTGTAATGTGTCCATTTAACTTATTTTTATAGCACTTAGGCAATATTGTTAGTCTTAGTGAGTAGTTCACATCTTTACAAAAGCATGCTCTCCCTATCCATTGGGCCCACAATAACACTCTCTTTGAGGCCATTCTGAATCCTGTCTCGTGTAATGATAATATATTATGAAAACAGATACTTTAAGAATTTCCTGTACAGCAGTCAGTTGTTTATTCTCTCTCTCTCTCTCTCTCTCTCTCTCCCTCCCCCACCCCAGCTTCTTTTTCTGTGACTTTGTTTTTCATAAAGAGAAGGCATCTCCTGAATACAATCGCTTTGTTCTGAAGACATCGTGAACTATTAATTCTTAACCCTTTGACAAAACTAGTGAAGTTGTTTTCTGTATCTTTTGCTTCATCTGTCTTTATAGAGTGACCTAGGAATTCAAGTGTAAGTTGTTTCCATTGTTGAACTGGATATTTATATACTTGGTATGCTTTTCACGTGTTATTTAATTCTGTATAATTTCCTATATTTGTATTAAAATATTGAGCAATTAAAAGTGTCAACTAAATATTTGATGTGGCATTCCCTTGAGAAATATAGAAATAAAGAATAAAAAAAAAAAAAAAAAA (SEQ ID NO: 27) >NP_034948.3 OX-2 membrane glycoprotein isoform 1precursor [Mus musculus]MGSLVFRRPFCHLSTYSLIWGMAAVALSTAQVEVVTQDERKALHTTASLRCSLKTSQEPLIVTWQKKKAVSPENMVTYSKTHGVVIQPAYKDRINVTELGLWNSSITFWNTTLEDEGCYMCLENTFGSQKVSGTACLTLYVQPIVHLHYNYFEDHLNITCSATARPAPAISWKGTGTGIENSTESHFHSNGTTSVTSILRVKDPKTQVGKEVICQVLYLGNVIDYKQSLDKGFWFSVPLLLSIVSLVILLILISILLYWKRHRNQERGESSQGMQRMK (SEQ ID NO: 28) Human>NM_009587.3 Homo sapiens galectin 9 (LGALS9), transcript Galectin-9variant 1, mRNACTTTGTTAAGTCGTTCCCTCTACAAAGGACTTCCTAGTGGGTGTGAAAGGCAGCGGTGGCCACAGAGGCGGCGGAGAGATGGCCTTCAGCGGTTCCCAGGCTCCCTACCTGAGTCCAGCTGTCCCCTTTTCTGGGACTATTCAAGGAGGTCTCCAGGACGGACTTCAGATCACTGTCAATGGGACCGTTCTCAGCTCCAGTGGAACCAGGTTTGCTGTGAACTTTCAGACTGGCTTCAGTGGAAATGACATTGCCTTCCACTTCAACCCTCGGTTTGAAGATGGAGGGTACGTGGTGTGCAACACGAGGCAGAACGGAAGCTGGGGGCCCGAGGAGAGGAAGACACACATGCCTTTCCAGAAGGGGATGCCCTTTGACCTCTGCTTCCTGGTGCAGAGCTCAGATTTCAAGGTGATGGTGAACGGGATCCTCTTCGTGCAGTACTTCCACCGCGTGCCCTTCCACCGTGTGGACACCATCTCCGTCAATGGCTCTGTGCAGCTGTCCTACATCAGCTTCCAGAACCCCCGCACAGTCCCTGTTCAGCCTGCCTTCTCCACGGTGCCGTTCTCCCAGCCTGTCTGTTTCCCACCCAGGCCCAGGGGGCGCAGACAAAAACCTCCCGGCGTGTGGCCTGCCAACCCGGCTCCCATTACCCAGACAGTCATCCACACAGTGCAGAGCGCCCCTGGACAGATGTTCTCTACTCCCGCCATCCCACCTATGATGTACCCCCACCCCGCCTATCCGATGCCTTTCATCACCACCATTCTGGGAGGGCTGTACCCATCCAAGTCCATCCTCCTGTCAGGCACTGTCCTGCCCAGTGCTCAGAGGTTCCACATCAACCTGTGCTCTGGGAACCACATCGCCTTCCACCTGAACCCCCGTTTTGATGAGAATGCTGTGGTCCGCAACACCCAGATCGACAACTCCTGGGGGTCTGAGGAGCGAAGTCTGCCCCGAAAAATGCCCTTCGTCCGTGGCCAGAGCTTCTCAGTGTGGATCTTGTGTGAAGCTCACTGCCTCAAGGTGGCCGTGGATGGTCAGCACCTGTTTGAATACTACCATCGCCTGAGGAACCTGCCCACCATCAACAGACTGGAAGTGGGGGGCGACATCCAGCTGACCCATGTGCAGACATAGGCGGCTTCCTGGCCCTGGGGCCGGGGGCTGGGGTGTGGGGCAGTCTGGGTCCTCTCATCATCCCCACTTCCCAGGCCCAGCCTTTCCAACCCTGCCTGGGATCTGGGCTTTAATGCAGAGGCCATGTCCTTGTCTGGTCCTGCTTCTGGCTACAGCCACCCTGGAACGGAGAAGGCAGCTGACGGGGATTGCCTTCCTCAGCCGCAGCAGCACCTGGGGCTCCAGCTGCTGGAATCCTACCATCCCAGGAGGCAGGCACAGCCAGGGAGAGGGGAGGAGTGGGCAGTGAAGATGAAGCCCCATGCTCAGTCCCCTCCCATCCCCCACGCAGCTCCACCCCAGTCCCAAGCCACCAGCTGTCTGCTCCTGGTGGGAGGTGGCCTCCTCAGCCCCTCCTCTCTGACCTTTAACCTCACTCTCACCTTGCACCGTGCACCAACCCTTCACCCCTCCTGGAAAGCAGGCCTGATGGCTTCCCACTGGCCTCCACCACCTGACCAGAGTGTTCTCTTCAGAGGACTGGCTCCTTTCCCAGTGTCCTTAAAATAAAGAAATGAAAATGCTTGTTGGCACATTCA (SEQ ID NO: 29)>NP_033665.1 galectin-9 isoform long [Homo sapiens]MAFSGSQAPYLSPAVPFSGTIQGGLQDGLQITVNGTVLSSSGTRFAVNFQTGFSGNDIAFHFNPRFEDGGYVVCNTRQNGSWGPEERKTHMPFQKGMPFDLCFLVQSSDFKVMVNGILFVQYFHRVPFHRVDTISVNGSVQLSYISFQNPRTVPVQPAFSTVPFSQPVCFPPRPRGRRQKPPGVWPANPAPITQTVIHTVQSAPGQMFSTPAIPPMMYPHPAYPMPFITTILGGLYPSKSILLSGTVLPSAQRFHINLCSGNHIAFHLNPRFDENAVVRNTQIDNSWGSEERSLPRKMPFVRGQSFSVWILCEAHCLKVAVDGQHLFEYYHRLRNLPTINRLEVGGDIQLTHVQT (SEQ ID NO: 30) Mouse>NM_010708.2 Mus musculus lectin, galactose binding, Galectin-9soluble 9 (Lgals9), transcript variant 1, mRNAGCCAAATAGCTGTGGTTTCTGTTTCCTAGCTCAGCCCTGCCCTGCGCAGAGTTCTGTCGTCCACCATCGAGTGAGGAAGAGAGCATTGGTTCCCCTGAGATAGAAGAGATGGCTCTCTTCAGTGCCCAGTCTCCATACATTAACCCGATCATCCCCTTTACTGGACCAATCCAAGGAGGGCTGCAGGAGGGACTTCAGGTGACCCTCCAGGGGACTACCAAGAGTTTTGCACAAAGGTTTGTGGTGAACTTTCAGAACAGCTTCAATGGAAATGACATTGCCTTCCACTTCAACCCCCGGTTTGAGGAAGGAGGGTATGTGGTTTGCAACACGAAGCAGAACGGACAGTGGGGTCCTGAGGAGAGAAAGATGCAGATGCCCTTCCAGAAGGGGATGCCCTTTGAGCTTTGCTTCCTGGTGCAGAGGTCAGAGTTCAAGGTGATGGTGAACAAGAAATTCTTTGTGCAGTACCAACACCGCGTACCCTACCACCTCGTGGACACCATCGCTGTCTCCGGCTGCTTGAAGCTGTCCTTTATCACCTTCCAGAACTCTGCAGCCCCTGTCCAGCATGTCTTCTCCACAGTGCAGTTCTCTCAGCCAGTCCAGTTCCCACGGACCCCTAAGGGGCGCAAACAGAAAACTCAGAACTTTCGTCCTGCCCACCAGGCACCCATGGCTCAAACTACCATCCATATGGTTCACAGCACCCCTGGACAGATGTTCTCTACTCCTGGAATCCCTCCTGTGGTGTACCCCACCCCAGCCTATACCATACCTTTCTACACCCCCATTCCAAATGGGCTTTACCCGTCCAAGTCCATCATGATATCAGGCAATGTCTTGCCAGATGCTACGAGGTTCCATATCAACCTTCGCTGTGGAGGTGACATTGCTTTCCACCTGAACCCCCGTTTCAATGAGAATGCTGTTGTCCGAAACACTCAGATCAACAACTCCTGGGGGCAGGAAGAGCGAAGTCTGCTTGGGAGGATGCCCTTCAGTCGAGGCCAGAGCTTCTCGGTGTGGATCATATGTGAAGGTCACTGCTTCAAGGTAGCTGTGAATGGTCAACACATGTGTGAATATTACCACCGCCTGAAGAACTTGCAGGATATCAACACTCTAGAAGTGGCGGGTGATATCCAGCTGACCCACGTGCAGACATAGGCAAGGTCTCTGGCCTAGGGATAAGGGCTGGAGCACTCTGCCTGTGTCTTATCTTTCCCCTGTCTCAGCCCTGGCACCATCAGAAGAGATCATCACTTATAGGAATTCCAGGAAGGTGAAATTCCCAATTGACTCCCTCCACAAAGGGGGTTTTCTAGGCTGTGTGGCACATGGCTGTCAGCCCATAGTCTGAGCCATTGCCCCCAAGCTAGCTATATACTGAGGGAAGTGACCCTCCTGGGTTTGCTCAGATCTCTGATCGTTCCCCCCTCTGTGGCCCTTTTCTTTCACCCCTCCAGGAGAGCCACCCTGATATCATCCCACTGGCCTCCAACTGACCCACAATGTCCACAGTAACTTTCCCCCATTCTCACCCAGTATCCATAAAATAAAGAAATAATATTGCTTGTCTACAC (SEQ ID NO: 31)>NP_034838.2 ga1ectin-9 isoform 1 [Mus musculus]MALFSAQSPYINPIIPFTGPIQGGLQEGLQVTLQGTTKSFAQRFVVNFQNSFNGNDIAFHFNPRFEEGGYVVCNTKQNGQWGPEERKMQMPFQKGMPFELCFLVQRSEFKVMVNKKFFVQYQHRVPYHLVDTIAVSGCLKLSFITFQNSAAPVQHVFSTVQFSQPVQFPRTPKGRKQKTQNFRPAHQAPMAQTTIHMVHSTPGQMFSTPGIPPVVYPTPAYTIPFYTPIPNGLYPSKSIMISGNVLPDATRFHINLRCGGDIAFHLNPRFNENAVVRNTQINNSWGQEERSLLGRMPFSRGQSFSVWIICEGHCFKVAVNGQHMCEYYHRLKNLQDINTLEVAGDIQLTHVQT (SEQ ID NO: 32) Human PVR>NM_006505.5 Homo sapiens PVR cell adhesion molecule (CD155)(PVR), transcript variant 1, mRNAAGTCACTTGTCTGGAGCTTGAAGAAGTGGGTATTCCCCTTCCCACCCCAGGCACTGGAGGAGCGGCCCCCCGGGGATTCCAGGACCTGAGCTCCGGGAGCTGGACTCGCAGCGACCGCGGCAGAGCGAGCGGGCGCCGGGAAGCGAGGAGACGCCCGCGGGAGGCCCAGCTGCTCGGAGCAACTGGCATGGCCCGAGCCATGGCCGCCGCGTGGCCGCTGCTGCTGGTGGCGCTACTGGTGCTGTCCTGGCCACCCCCAGGAACCGGGGACGTCGTCGTGCAGGCGCCCACCCAGGTGCCCGGCTTCTTGGGCGACTCCGTGACGCTGCCCTGCTACCTACAGGTGCCCAACATGGAGGTGACGCATGTGTCACAGCTGACTTGGGCGCGGCATGGTGAATCTGGCAGCATGGCCGTCTTCCACCAAACGCAGGGCCCCAGCTATTCGGAGTCCAAACGGCTGGAATTCGTGGCAGCCAGACTGGGCGCGGAGCTGCGGAATGCCTCGCTGAGGATGTTCGGGTTGCGCGTAGAGGATGAAGGCAACTACACCTGCCTGTTCGTCACGTTCCCGCAGGGCAGCAGGAGCGTGGATATCTGGCTCCGAGTGCTTGCCAAGCCCCAGAACACAGCTGAGGTTCAGAAGGTCCAGCTCACTGGAGAGCCAGTGCCCATGGCCCGCTGCGTCTCCACAGGGGGTCGCCCGCCAGCCCAAATCACCTGGCACTCAGACCTGGGCGGGATGCCCAATACGAGCCAGGTGCCAGGGTTCCTGTCTGGCACAGTCACTGTCACCAGCCTCTGGATATTGGTGCCCTCAAGCCAGGTGGACGGCAAGAATGTGACCTGCAAGGTGGAGCACGAGAGCTTTGAGAAGCCTCAGCTGCTGACTGTGAACCTCACCGTGTACTACCCCCCAGAGGTATCCATCTCTGGCTATGATAACAACTGGTACCTTGGCCAGAATGAGGCCACCCTGACCTGCGATGCTCGCAGCAACCCAGAGCCCACAGGCTATAATTGGAGCACGACCATGGGTCCCCTGCCACCCTTTGCTGTGGCCCAGGGCGCCCAGCTCCTGATCCGTCCTGTGGACAAACCAATCAACACAACTTTAATCTGCAACGTCACCAATGCCCTAGGAGCTCGCCAGGCAGAACTGACCGTCCAGGTCAAAGAGGGACCTCCCAGTGAGCACTCAGGCATGTCCCGTAACGCCATCATCTTCCTGGTTCTGGGAATCCTGGTTTTTCTGATCCTGCTGGGGATCGGGATTTATTTCTATTGGTCCAAATGTTCCCGTGAGGTCCTTTGGCACTGTCATCTGTGTCCCTCGAGTACAGAGCATGCCAGCGCCTCAGCTAATGGGCATGTCTCCTATTCAGCTGTGAGCAGAGAGAACAGCTCTTCCCAGGATCCACAGACAGAGGGCACAAGGTGACAGCGTCGGGACTGAGAGGGGAGAGAGACTGGAGCTGGCAAGGACGTGGGCCTCCAGAGTTGGACCCGACCCCAATGGATGAAGACCCCCTCCAAAGAGACCAGCCTCCCTCCCTGTGCCAGACCTCAAAACGACGGGGGCAGGTGCAAGTTCATAGGTCTCCAAGACCACCCTCCTTTCATTTGCTAGAAGGACTCACTAGACTCAGGAAAGCTGTTAGGCTCACAGTTACAGTTTATTACAGTAAAAGGACAGAGATTAAGATCAGCAAAGGGAGGAGGTGCACAGCACACGTTCCACGACAGATGAGGCGACGGCTTCCATCTGCCCTCTCCCAGTGGAGCCATATAGGCAGCACCTGATTCTCACAGCAACATGTGACAACATGCAAGAAGTACTGCCAATACTGCCAACCAGAGCAGCTCACTCGAGATCTTTGTGTCCAGAGTTTTTTGTTTGTCTTGAGACAGGGTCTGGCTCTGTTGGCAGACTAGAGTACAGTGGTGAGATCACAGTTCATTGCAGCCTTGACTTCTCAACGCCAAGTCATCCTCCCACCTCAGCCTCCTGAGTAGCTATGACTACAGGTATGTGCCACCACGTCTGGCTAATCTTTTTATTATTTGTAAAGTCGAGGTTTCCCTGTGTTGCCCAGGCTGGTCTTGAACTCTTGGCTCCAAGTGATACTTCTGCCTTGGCCTCCCAAAGTGCTGAATTAAGCAGCTCACCATCCACACGGCTGACCTCATACATCAAGCCAATACCGTGTGGCCCAAGACCCCCACCATAAATCACATCATTAGCATGAACCACCCAGAGTGGCCCAAGACTCCAAGATCAGCTACCAGGCAGGATATTCCAAGGGCTTAGAGATGAATGCCCAGGAGCTGAGGATAAAGGGCCCGATCTTTCTTTGGGCAAGGTTAAGCCTTTACTGCATAGCAGACCACACAGAAGGGTGTGGGCCACCAGAGAATTTTGGTAAAAATTTGGCCTCTGGCCTTGAGCTTCTAAATCTCTGTATCCGTCAGATCTCTGTGGTTACAAGAAACAGCCACTGACCCTGGTCACCAGAGGCTGCAATTCAGGCCGCAAGCAGCTGCCTGGGGGGTGTCCAAGGAGCAGAGAAAACTACTAGATGTGAACTTGAAGAAGGTTGTCAGCTGCAGCCACTTTCTGCCAGCATCTGCAGCCACTTTCTGCCAGCATCTGCAGCCAGCAAGCTGGGACTGGCAGGAAATAACCCACAAAAGAAGCAAATGCAATTTCCAACACAAGGGGGAAGGGATGCAGGGGGAGGCAGCGCTGCAGTTGCTCAGGACACGCTCCTATAGGACCAAGATGGATGCGACCCAAGACCCAGGAGGCCCAGCTGCTCAGTGCAACTGACAAGTTAAAAAGGTCTATGATCTTGAGGGCAGACAGCAGAATTCCTCTTATAAAGAAAACTGTTTGGGAAAATACGTTGAGGGAGAGAAGACCTTGGGCCAAGATGCTAAATGGGAATGCAAAGCTTGAGCTGCTCTGCAAGAGAAAATAAGCAGGACAGAGGATTTGCTCTGGACAGAGATGGAAGAGCCGGGAACAGAGAAGTGTGGGGAAGAGATAGGAACCAGCAGGATGGCAGGGGCAAAGGGCTCAAGGGTGAGGAGGCCAGTGGGACCCCACAGAGTTGGGGAGATAAAGGAACATTGGTTGCTTTGGTGGCACGTAAGCTCCTTGTCTGTCTCCAGCACCCAGAATCTCATTAAAGCTTATTTATTGTACCTCCAGCGGCTGTGTGCAATGGGGTCTTTTGTGGAAATCAAGGAGCAGACAGGTTTCATGTGTACTGTCACCACGTGGGATGGAACCAGAGGCATGGAAGCAAGACGCTAAATGAAGAGGGCCATAAGGGCTGGGATTCCCAGGCACCTTAGGAACAGCTTGTCTTTTTTTTTTTCCTCTCCAAAAAAAATGTTTAAGGGACGGTGTCTCCTGTCACCCAGGCTGGAGTGCAATGGCACGATCATAGCTCATTGCAGCCTCTAACTCCGGGGCTCAAGCAATCCTCCCACCTCAGCCTACCAAGTAGCTGTGACCACAGCTGCCCCTCACCATGCTAAGCTAATTTTTTTAATTAGATAGTACATAAACGTCCCAAAATTAGAAGATAAAAAGACATGAGGGATCCATTCTAATTTGTGTTTGGAGTGTAATGGTCCAGCTCCATTCTTCTGCACATGGATATCCAGTTTTACACAACACTGTGAATGTAATGAATGCCACTGAATCATACACTCAAAAATAGCTAAAATGGCAAATTGTCTGTTATCTCTTTTTAACCACCATTTTTGAAAATTAATTATACCAAAAAACCATTGAATAGTGCACTTTATTTATTTATTTATTTGTTTATTTATTTATTTATTTTAGAAATAAGAGTCTCACTTTGTTGCCCAGGCTGGAGTGCAGTGGCGTGATCATGGCTCATTGCAGCCTCGACCTGCTGGGCTCGGGCTATCCTTCCATCTCAGCCTCCCGAGTAGCTGGGACTATAGGTGGGCGCCACCCCACCTGGCTAAATCTCTTTTTAACTTTTGTAGAGATAGGCATCTCGCTATGTTGCCTAGGCTGGGCTGGAACTCCTGGGCTCAAGTGCTCCTCCTGCCTTGGCCTCCCAAAGCGCTAGGATTACAGATGTGAGCCACCGCGCCCACCCTGAACCTTACTTTTTTTGCTCAGTTTCTGGTAATTCAGAGAATGCCTCCTGAGTTGTTCTACACCCACCTCATATTCCATGGGAGGGCTGTACAGGGCTTTTTTAACGAGGCCTCTAAGGACAGGCATTTGTATCCTTTCCAGCCTTTCACTATTACAATGTTGTAGTGAATAACTTTACACACTGTCATTTATTTTACTTTTTTTTTTTTTTATTTTAGAGAAAGGAATCTTGCCATCTTGCCCAGGCTGGTCTCAAATTCCTGGGCCCAAACAATCCTCCCGCCTTGGCCTCCTAAAGTACTGGGATTTATAGGCATAAGCCACCGTGCCTGGCCAATGCACACTGTCATTTAGCTCATGTTAACACCTGAGTGTAGGACACACTCCTGGAGGTGGAATTGCTGGGCCAAAGAGTATGTTTCTTGTCATTGTGATAGATATTGACAAATGAACCCTCACAGAAGTTGTGCTGAGTTCTGTTCCCACCAGCGACGTAGGCGATGACCTTTTTCTGGAGGGAGGGGGCATCCTTGGAGTCCACAGAGCCAGGAATGGAGAGTGGGCCCAGAATTTTGGTATAGGTGTTGTATAAACTTATAGTAAGGTTAAGAAAACCGCAACTATCCTTATCAGAGACTTGGCGGGGGGCAGGGTATGATGGAGATCATAAGGAGGCTAAAACACTCCACACCCTCCCTCTGCATTGCTCCTGCACGGGAGTCGGGAATCTTTTCAGGTTGATACGATCTCACCTTGAGGAGCTGTGAGGTCCCAGAAGCCTCTGGGTTGCAGATTGCTTGGGGTGAAAATGTCTGTGCTACTGAAATCTAACTTTTTACAAAAAATTACGGGCTGGGCGCAGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCTGCAGCGGGTGGATCACTTGAGGTAAGGAGTTCAAGACCAGACCATAGTGAAACCGTGTCTCTACAAAAAAAATTAGCCAGGTGTGGTGGTGCATGCTTGTAATCCCAGCTACTCAGAAGGCTGAGGTGGGAGAATCCCTTGAACCCGGGAAGTGGAGGCTGGAGTAAACCATGATCGAGTTACTGCACTCCAGCCTGGGTGACAAGAGTGAGACTCTGTCTCCAAAAAAAAAAAAAAAAAAAAAAAAACTGGATTGCCTGGCTCTACTCCGGGCACAGCATGCAGGCCCAGTTCTGCTGCTCTGCTGTTTGTTCTGCTTTCCTCCACATATTGGCATCACCCTCTGGTGCCAAGATGGCTGCTGCATTCCAGGCATCACATCCAGACTCAGACCCAGAGAAGCTGCCCATCCCTACCTGGGTGAGCCTTTGTAGGAACGAGAAACCGCATCCAGCAGCAGAAACCTCACCCAGCAGCGTCTTTTCCGGTCTCATTCACCAGCGCCGCCCACCGCTCAACCAATCCCTGGCCAAAAGAATGGGACCGCCTGGAAGGCTGGACCAAACAGGACCTGCCCTCTGGGGCTGGGGAGAGGCCCAGATGAAGGCTGCAGGACAGGATGGACTCCTAGACCTCTGTTACCAGCAGTGACTACCTCTGTCTGGGTGGTTGGAACATGTTTGAATTTTATTCTAAGTACTGTCTACAAGTTCTGCAATAAACCTTGACTCTTCTTTTAATAATGCAAAA (SEQ ID NO: 33) >NP_006496.4 poliovirus receptor isoform alpha precursor[Homo sapiens] MARAMAAAWPLLLVALLVLSWPPPGTGDVVVQAPTQVPGFLGDSVTLPCYLQVPNMEVTHVSQLTWARHGESGSMAVFHQTQGPSYSESKRLEFVAARLGAELRNASLRMFGLRVEDEGNYTCLFVTFPQGSRSVDIWLRVLAKPQNTAEVQKVQLTGEPVPMARCVSTGGRPPAQITWHSDLGGMPNTSQVPGFLSGTVTVTSLWILVPSSQVDGKNVTCKVEHESFEKPQLLTVNLTVYYPPEVSISGYDNNWYLGQNEATLTCDARSNPEPTGYNWSTTMGPLPPFAVAQGAQLLIRPVDKPINTTLICNVTNALGARQAELTVQVKEGPPSEHSGMSRNAIIFLVLGILVFLILLGIGIYFYWSKCSREVLWHCHLCPSSTEHASASANGHVSYSAVSRENSSSQDPQTEGTR (SEQ ID NO: 34) Mouse PVR>NM_027514.2 Mus musculus poliovirus receptor (Pvr), mRNA (CD155)AGGCGGCACCCGCTTAGCTGAGATTCCAGCACTTGACTTCAGGGTTTCGGAGAGATAAGGCGCTTGGCCGTTACTAACTGGACTACAAAGAGCTGGATCGGACCGGAACCACATGGCTCAACTCGCCCGAGCCACCCGCTCCCCGCTGTCATGGCTGCTGCTGCTGTTCTGCTATGCACTCCGGAAAGCGGGTGGGGATATACGTGTGCTGGTGCCCTACAATTCGACAGGCGTCTTGGGAGGGTCGACCACCTTGCACTGTAGTCTGACTTCTAATGAGAATGTGACTATCACTCAAATAACCTGGATGAAGAAGGATTCAGGTGGATCCCACGCTCTTGTGGCTGTCTTCCACCCCAAGAAGGGGCCCAACATCAAAGAGCCAGAGAGGGTGAAATTCTTGGCTGCCCAACAGGATCTGAGGAACGCATCTCTGGCCATCTCGAACTTAAGTGTAGAAGACGAAGGCATCTATGAATGTCAGATTGCCACATTCCCCAGAGGCAGTAGAAGCACCAATGCCTGGCTGAAGGTGCAAGCCCGACCTAAGAACACTGCAGAGGCCCTGGAGCCCTCTCCCACCTTGATACTGCAGGATGTGGCTAAATGCATCTCTGCCAATGGTCACCCTCCTGGACGAATCTCTTGGCCCTCGAATGTGAATGGAAGTCACCGTGAAATGAAGGAACCAGGGTCCCAGCCGGGCACCACCACAGTTACCAGCTACCTCTCCATGGTACCTTCTCGCCAGGCAGACGGCAAGAACATCACCTGCACGGTGGAGCATGAAAGCTTACAGGAGCTGGACCAGCTGCTGGTGACCCTTTCCCAACCCTATCCACCTGAAAACGTGTCCATCTCTGGCTATGACGGCAACTGGTATGTTGGCCTCACTAACTTGACCCTGACCTGTGAAGCTCACAGCAAACCAGCGCCTGACATGGCTGGATATAACTGGAGCACGAACACGGGTGACTTTCCCAACTCTGTTAAGCGCCAGGGCAATATGCTTCTAATCTCCACCGTAGAGGATGGTCTCAATAACACGGTCATTGTGTGCGAAGTCACCAATGCCCTAGGGTCTGGGCAGGGCCAAGTGCACATCATTGTTAAAGAGAAACCTGAGAATATGCAGCAAAATACAAGATTACACCTAGGCTACATCTTTCTTATCGTCTTTGTCCTCGCTGTAGTCATCATCATCGCAGCACTATACACTATACGAAGATGCAGGCATGGTCGTGCTCTGCAGTCCAATCCCTCAGAGAGGGAGAACGTCCAGTATTCATCTGTGAACGGCGACTGTAGACTGAACATGGAGCCAAACAGCACAAGGTGACGGTGCTGGGTAGACAGAACTAAGGAACTTGAAGGCATAGCAACTGGAACCCTACTCTCATAAATGAAGAAGCCTCCAGAGAGACTGGCTGCTCAGTGTGATGAGCATAGCAAGTTTGGGGGGTCTCCCAGGATGCTGCCGAATTCCACGTTGTCAAAAGGACCCATGGAGGCCAGTGTGTTGGCTCACTCTTGACATCTCAGCAAGCTGGGGGGGGGGGGGGGAGCATAAAGCAAGGTTGAGTCTAGCTTGGGCTATAGAGCAAAGCCCTGTCCATACACAAACAAGCTAAGGGGCTTTGAGACGGTCAGAAACTGAAGTCTTGCTTTGGGTAAGGTAAATCCTCTACCGCATGTATGTGCTAGACTTGAAAGACTTCCACACAGACCTCTTTATAAGTTGACTCCATTGGGGCTATCCCCTCCTCTCTGGACAAGGTCTCTGTATGTAGCCAAGGCTAGGCTCAAACTCACAGAGATATGTCTGCTTCTACCTCCCCAGTGCTAGAGTTGAAAGTATTTGTGCCACTGCACTTTTCTAGGTCTTCTTTTAATGAAGTAAAGTATATATTTATAAAAAGCTATTTAGTTATATATATATATATTTTTGAGACTATTTCATAGAGCCCAAGCTAACCTCAAACTTACTATGTAGCCAAGAGTGATGGTAAACTAATTTATTTTAATTTATTTGTCTTCAATTTTAACCATCACCCAACCCCTGCTCCCTTCCATATCTTCTTTCAATCCATTTCATTGTCTTTTTCTTCCCAGACACTATTCTGACTTACGTCTCCATTACAAACATTTTATTGAACTACATAAAAATGTGTGAACCACAAAAAAAAAATGTATTTGTCAAAATTGTAGTTGTCTTTCTGAGGCTGACCTGAGTTCTCTGATACCATTCTCTCCAGTTGTATCCAGTTTCCTGTAAACAATGTGACTTTGTTTTTCTCAGTAGCTAAAACATCCCAATTATGTGAGTGTACACTTTCTTTACTCATTCCTCTGTGGGCCACCAGCTGGGTTGGTTCCATATCTGAGCTATTGTGCATGGAATTGTCTCTGTGGTGGGTTTAGTAAACTCCCAGGAATGCCTGTACATGTTTGTAGAGGCCAGAAGAAGGCACAAAATCTTGAGCCAGGCTTACATGCACTTGTGAGTAGCCCCACATAGGTGCTAAGAACCCAGTTCAGGTCCTCTGCTGTGGGATGGTGGGCTGTGCACAGAAAGCCTGGTCCCGGTCTAGCAAAGGTCTGGAACTCCGGAGCCGGTGGGCTGTGATTTACACCAGCATGGGATGGAAGGAGTTGGACCTCGCCTCCTGGGCACCTGGCTCCTGTCACATAGCTACAGCCTCCCACAGCCCCCCTATAGGGAGGTATGCAGCATCAATCACATAGTAGCTGCACTAAGCCCTCCCACATGCAAATAAGGTTTCCCCAAACTCTCAGTCCAAGCCAATGAAAAGTACCTGCTGTCAAACCCTAAATCATCCCCAAAACTCTGTAAGTCCTATCAGGGAATAAAATGTGTGTGAAAACTAAAAAAAAAAAAAAA (SEQ ID NO: 35)>NP_081790.1 poliovirus receptor precursor [Mus musculus]MAQLARATRSPLSWLLLLFCYALRKAGGDIRVLVPYNSTGVLGGSTTLHCSLTSNENVTITQITWMKKDSGGSHALVAVFHPKKGPNIKEPERVKFLAAQQDLRNASLAISNLSVEDEGIYECQIATFPRGSRSTNAWLKVQARPKNTAEALEPSPTLILQDVAKCISANGHPPGRISWPSNVNGSHREMKEPGSQPGTTTVTSYLSMVPSRQADGKNITCTVEHESLQELDQLLVTLSQPYPPENVSISGYDGNWYVGLTNLTLTCEAHSKPAPDMAGYNWSTNTGDFPNSVKRQGNMLLISTVEDGLNNTVIVCEVTNALGSGQGQVHIIVKEKPENMQQNTRLHLGYIFLIVFVLAVVIIIAALYTIRRCRHGRALQSNPSERENVQYSSVNGDCRLNMEPNSTR (SEQ ID NO: 36) Human>NM_002856.3 Homo sapiens nectin cell adhesion molecule 2 Nectin-2(NECTIN2), transcript variant alpha, mRNA (CD112)GTGACGTCAGCGGGTTCGAACCGCCGGAGCTGAGCGAGAGGCCGGGGGTGCCGAGCC isoform alphaGGGCGGGGAGAGCTGGGCCGGGAGAGCAGAACAGGGAGGCTAGAGCGCAGCGGGAACCGGCCCGGAGCCGGAGCCGGAGCCCCACAGGCACCTACTAAACCGCCCAGCCGATCGGCCCCCACAGAGTGGCCCGCGGGCCTCCGGCCGGGCCCAGTCCCCTCCCGGGCCCTCCATGGCCCGGGCCGCTGCCCTCCTGCCGTCGAGATCGCCGCCGACGCCGCTGCTGTGGCCGCTGCTGCTGCTGCTGCTCCTGGAAACCGGAGCCCAGGATGTGCGAGTTCAAGTGCTACCCGAGGTGCGAGGCCAGCTCGGGGGCACCGTGGAGCTGCCGTGCCACCTGCTGCCACCTGTTCCTGGACTGTACATCTCCCTGGTGACCTGGCAGCGCCCAGATGCACCTGCGAACCACCAGAATGTGGCCGCCTTCCACCCTAAGATGGGTCCCAGCTTCCCCAGCCCGAAGCCTGGCAGCGAGCGGCTGTCCTTCGTCTCTGCCAAGCAGAGCACTGGGCAAGACACAGAGGCAGAGCTCCAGGACGCCACGCTGGCCCTCCACGGGCTCACGGTGGAGGACGAGGGCAACTACACTTGCGAGTTTGCCACCTTCCCCAAGGGGTCCGTCCGAGGGATGACCTGGCTCAGAGTCATAGCCAAGCCCAAGAACCAAGCTGAGGCCCAGAAGGTCACGTTCAGCCAGGACCCTACGACAGTGGCCCTCTGCATCTCCAAAGAGGGCCGCCCACCTGCCCGGATCTCCTGGCTCTCATCCCTGGACTGGGAAGCCAAAGAGACTCAGGTGTCAGGGACCCTGGCCGGAACTGTCACTGTCACCAGCCGCTTCACCTTGGTGCCCTCGGGCCGAGCAGATGGTGTCACGGTCACCTGCAAAGTGGAGCATGAGAGCTTCGAGGAACCAGCCCTGATACCTGTGACCCTCTCTGTACGCTACCCTCCTGAAGTGTCCATCTCCGGCTATGATGACAACTGGTACCTCGGCCGTACTGATGCCACCCTGAGCTGTGACGTCCGCAGCAACCCAGAGCCCACGGGCTATGACTGGAGCACGACCTCAGGCACCTTCCCGACCTCCGCAGTGGCCCAGGGCTCCCAGCTGGTCATCCACGCAGTGGACAGTCTGTTCAATACCACCTTCGTCTGCACAGTCACCAATGCCGTGGGCATGGGCCGCGCTGAGCAGGTCATCTTTGTCCGAGAAACCCCCAGGGCCTCGCCCCGAGATGTGGGCCCGCTGGTGTGGGGGGCCGTGGGGGGGACACTGCTGGTGCTGCTGCTTCTGGCTGGGGGGTCCTTGGCCTTCATCCTGCTGAGGGTGAGGAGGAGGAGGAAGAGCCCTGGAGGAGCAGGAGGAGGAGCCAGTGGCGACGGGGGATTCTACGATCCGAAAGCTCAGGTGTTGGGAAATGGGGACCCCGTCTTCTGGACACCAGTAGTCCCTGGTCCCATGGAACCAGATGGCAAGGATGAGGAGGAGGAGGAGGAGGAAGAGAAGGCAGAGAAAGGCCTCATGTTGCCTCCACCCCCAGCACTCGAGGATGACATGGAGTCCCAGCTGGACGGCTCCCTCATCTCACGGCGGGCAGTTTATGTGTGACCTGGACACAGACAGAGACAGAGCCAGGCCCGGCCCTCCCGCCCCCGACCTGACCACGCCGGCCTAGGGTTCCAGACTGGTTGGACTTGTTCGTCTGGACGACACTGGAGTGGAACACTGCCTCCCACTTTCTTGGGACTTGGAGGGAGGTGGAACAGCACACTGGACTTCTCCCGTCTCTAGGGCTGCATGGGGAGCCCGGGGAGCTGAGTAGTGGGGATCCAGAGAGGACCCCCGCCCCCAGAGACTTGGTTTTGGCTCCAGCCTTCCCCTGGCCCCGTGACACTCAGGAGTTAATAAATGCCTTGGAGGAAAACA (SEQ ID NO: 37)>NP_002847.1 nectin-2 isoform alpha precursor [Homo sapiens]MARAAALLPSRSPPTPLLWPLLLLLLLETGAQDVRVQVLPEVRGQLGGTVELPCHLLPPVPGLYISLVTWQRPDAPANHQNVAAFHPKMGPSFPSPKPGSERLSFVSAKQSTGQDTEAELQDATLALHGLTVEDEGNYTCEFATFPKGSVRGMTWLRVIAKPKNQAEAQKVTFSQDPTTVALCISKEGRPPARISWLSSLDWEAKETQVSGTLAGTVTVTSRFTLVPSGRADGVTVTCKVEHESFEEPALIPVTLSVRYPPEVSISGYDDNWYLGRTDATLSCDVRSNPEPTGYDWSTTSGTFPTSAVAQGSQLVIHAVDSLFNTTFVCTVTNAVGMGRAEQVIFVRETPRASPRDVGPLVWGAVGGTLLVLLLLAGGSLAFILLRVRRRRKSPGGAGGGASGDGGFYDPKAQVLGNGDPVFWTPVVPGPMEPDGKDEEEEEEEEKAEKGLMLPPPPALEDDMESQLDGSLISRRAVYV (SEQ ID NO: 38) Mouse Nectin->NM_001159724.1 Mus musculus nectin cell adhesion 2 (CD112)molecule 2 (Nectin2), transcript variant 2, mRNA isoform alphaGAGCCCTAGGATCGGCTTGGCGAAGAGGGGCGGGGCCTGTGACGTCATGAGTCCGGCCCGCTGGAGCTAAGCGAGGGGCCGGGGGGCGCGGATCCTGAGAGCCAGGCGAGGGAAAGCTGGGCCGAACGAACTGATCCGGGGAGCCGTGAGCGGCGGAAGCCGGCCTGGAGCCGGACACTTCAGACCCCTGACTGCCCTCCCAGCCGATCGGTACACGAAGAGTGGTCCCTAGGCACCCCCTGCCCGGGCCCAGTCCCTCCCCGGGCCCCCCATGGCCCGGGCCGCAGTCCTCCCGCCGTCCAGATTGTCACCGACGCTGCCGTTGTTGCCGCTGCTACTGCTCCTGCTTCAGGAAACAGGAGCCCAAGATGTGCGGGTACGAGTGCTTCCCGAGGTCCGGGGCCGCTTGGGAGGCACCGTGGAGTTACCGTGCCACCTGCTCCCACCCACGACGGAGCGCGTCTCTCAGGTGACCTGGCAGCGCCTGGATGGCACAGTTGTGGCTGCTTTCCACCCATCCTTCGGAGTGGATTTCCCCAACTCTCAGTTCAGCAAGGACCGTCTGTCCTTTGTCAGAGCGAGACCAGAAACAAACGCAGACCTGCGGGATGCCACACTGGCCTTCCGGGGACTGAGGGTAGAGGACGAGGGCAATTACACCTGCGAGTTTGCCACGTTTCCCAACGGTACCCGCAGGGGGGTGACCTGGCTCAGAGTCATAGCCCAGCCTGAGAACCACGCTGAAGCCCAGGAGGTCACAATTGGCCCCCAGTCGGTGGCTGTAGCCCGCTGTGTCTCCACTGGGGGCCGCCCCCCTGCCCGAATCACCTGGATCTCATCTCTGGGTGGAGAGGCCAAAGATACTCAGGAGCCAGGGATACAGGCTGGCACCGTCACTATCATCAGCCGATACTCCTTGGTGCCCGTGGGCCGAGCGGATGGCGTCAAGGTCACGTGTAGAGTGGAACACGAGAGCTTCGAAGAGCCGATCCTGCTGCCAGTGACCCTCTCTGTGCGCTACCCTCCAGAAGTATCCATCTCCGGCTATGATGACAACTGGTACCTTGGCCGCAGTGAGGCCATACTGACCTGTGATGTACGAAGCAACCCAGAGCCCACAGACTATGACTGGAGCACGACCTCGGGCGTCTTCCCAGCCTCTGCAGTGGCCCAGGGCTCTCAGCTGCTTGTCCACTCTGTGGATCGAATGGTCAACACTACCTTCATCTGTACAGCCACCAACGCTGTGGGGACAGGCCGTGCTGAGCAGGTCATCCTGGTGCGAGACACCCCCCAGGCCTCCCGAGATGTGGGTCCGCTGGTGTGGGGGGCCGTGGGGGGAACATTGCTGGTGCTACTCCTGGCTGGGGGGTTCCTGGCCTTGATCCTGCTGAGGGGGAGGAGGAGGCGGAAGAGCCCTGGAGGAGGAGGAAATGATGGCGACAGAGGATCCTACGATCCAAAGACTCAGGTGTTTGGGAACGGGGGTCCTGTCTTCTGGAGGTCAGCATCCCCTGAGCCCATGAGGCCAGATGGCAGGGAGGAAGATGAGGAGGAGGAGGAAGAAATGAAGGCAGAGGAAGGTCTCATGCTACCTCCACACGAGTCACCTAAGGACGACATGGAGTCCCATCTGGATGGCTCCCTCATCTCTCGGCGGGCAGTTTACGTGTGACCCTACGATATAGACACTGGACACATGGAAACACCAAGTTCCACCCTCACTGCCAACCACACCAATGCCAGCCAGCAACGATGGCTAGGGACCGGTTGGACTGGTTCTTCTGGGGCACACTGGAGTTGGAAGGGCACCGCCCCTGCTTTCAGGATAGAGGACAAGTGGAACCACACAGACTCCTATCTTTAGGGCCTCATGGAGTAGGGGACCCCAGGAGCGCCATGGTGCACACTCAGGACTCCTCAGAGCTTGCTTTCGGCCCCAGCCTAGCCCTGGCCCCGAAACACTCAGGAGCTAATAAATGCCTTGTCGGAAAAAAAAAAAAAAAAAA (SEQ ID NO: 39) >NP_001153196.1 nectin-2 isoform 2 precursor [Musmusculus] MARAAVLPPSRLSPTLPLLPLLLLLLQETGAQDVRVRVLPEVRGRLGGTVELPCHLLPPTTERVSQVTWQRLDGTVVAAFHPSFGVDFPNSQFSKDRLSFVRARPETNADLRDATLAFRGLRVEDEGNYTCEFATFPNGTRRGVTWLRVIAQPENHAEAQEVTIGPQSVAVARCVSTGGRPPARITWISSLGGEAKDTQEPGIQAGTVTIISRYSLVPVGRADGVKVTCRVEHESFEEPILLPVTLSVRYPPEVSISGYDDNWYLGRSEAILTCDVRSNPEPTDYDWSTTSGVFPASAVAQGSQLLVHSVDRMVNTTFICTATNAVGTGRAEQVILVRDTPQASRDVGPLVWGAVGGTLLVLLLAGGFLALILLRGRRRRKSPGGGGNDGDRGSYDPKTQVFGNGGPVFWRSASPEPMRPDGREEDEEEEEEMKAEEGLMLPPHESPKDDMESHLDGSLISRRAVYV (SEQ ID NO: 40) Human>NM_001042724.2 Homo sapiens nectin cell adhesion Nectin-2molecule 2 (NECTIN2), transcript variant delta, mRNA (CD112)GTGACGTCAGCGGGTTCGAACCGCCGGAGCTGAGCGAGAGGCCGGGGGTGCCGAGCC isoform deltaGGGCGGGGAGAGCTGGGCCGGGAGAGCAGAACAGGGAGGCTAGAGCGCAGCGGGAACCGGCCCGGAGCCGGAGCCGGAGCCCCACAGGCACCTACTAAACCGCCCAGCCGATCGGCCCCCACAGAGTGGCCCGCGGGCCTCCGGCCGGGCCCAGTCCCCTCCCGGGCCCTCCATGGCCCGGGCCGCTGCCCTCCTGCCGTCGAGATCGCCGCCGACGCCGCTGCTGTGGCCGCTGCTGCTGCTGCTGCTCCTGGAAACCGGAGCCCAGGATGTGCGAGTTCAAGTGCTACCCGAGGTGCGAGGCCAGCTCGGGGGCACCGTGGAGCTGCCGTGCCACCTGCTGCCACCTGTTCCTGGACTGTACATCTCCCTGGTGACCTGGCAGCGCCCAGATGCACCTGCGAACCACCAGAATGTGGCCGCCTTCCACCCTAAGATGGGTCCCAGCTTCCCCAGCCCGAAGCCTGGCAGCGAGCGGCTGTCCTTCGTCTCTGCCAAGCAGAGCACTGGGCAAGACACAGAGGCAGAGCTCCAGGACGCCACGCTGGCCCTCCACGGGCTCACGGTGGAGGACGAGGGCAACTACACTTGCGAGTTTGCCACCTTCCCCAAGGGGTCCGTCCGAGGGATGACCTGGCTCAGAGTCATAGCCAAGCCCAAGAACCAAGCTGAGGCCCAGAAGGTCACGTTCAGCCAGGACCCTACGACAGTGGCCCTCTGCATCTCCAAAGAGGGCCGCCCACCTGCCCGGATCTCCTGGCTCTCATCCCTGGACTGGGAAGCCAAAGAGACTCAGGTGTCAGGGACCCTGGCCGGAACTGTCACTGTCACCAGCCGCTTCACCTTGGTGCCCTCGGGCCGAGCAGATGGTGTCACGGTCACCTGCAAAGTGGAGCATGAGAGCTTCGAGGAACCAGCCCTGATACCTGTGACCCTCTCTGTACGCTACCCTCCTGAAGTGTCCATCTCCGGCTATGATGACAACTGGTACCTCGGCCGTACTGATGCCACCCTGAGCTGTGACGTCCGCAGCAACCCAGAGCCCACGGGCTATGACTGGAGCACGACCTCAGGCACCTTCCCGACCTCCGCAGTGGCCCAGGGCTCCCAGCTGGTCATCCACGCAGTGGACAGTCTGTTCAATACCACCTTCGTCTGCACAGTCACCAATGCCGTGGGCATGGGCCGCGCTGAGCAGGTCATCTTTGTCCGAGAGACCCCCAACACAGCAGGCGCAGGGGCCACAGGCGGCATCATCGGGGGCATCATCGCCGCCATCATTGCTACTGCTGTGGCTGCCACGGGCATCCTTATCTGCCGGCAGCAGCGGAAGGAGCAGACGCTGCAGGGGGCAGAGGAGGACGAAGACCTGGAGGGACCTCCCTCCTACAAGCCACCGACCCCAAAAGCGAAGCTGGAGGCACAGGAGATGCCCTCCCAGCTCTTCACTCTGGGGGCCTCGGAGCACAGCCCACTCAAGACCCCCTACTTTGATGCTGGCGCCTCATGCACTGAGCAGGAAATGCCTCGATACCATGAGCTGCCCACCTTGGAAGAACGGTCAGGACCCTTGCACCCTGGAGCCACAAGCCTGGGGTCCCCCATCCCGGTGCCTCCAGGGCCACCTGCTGTGGAAGACGTTTCCCTGGATCTAGAGGATGAGGAGGGGGAGGAGGAGGAAGAGTATCTGGACAAGATCAACCCCATCTATGATGCTCTGTCCTATAGCAGCCCCTCTGATTCCTACCAGGGCAAAGGCTTTGTCATGTCCCGGGCCATGTATGTGTGAGCTGCCATGCGCCTGGCGTCTCACATCTCACCTGTTGATCCCTTAGCTTTCTTGCCAAGGATCTAGTGCCCCCTGACCTCTGGCCAGGCCACTGTCAGTTAACACATATGCATTCCATTTGTGATGTCTACCTTGGTGGCTCCACTATGACCCCTAACCCATGAGCCCAGAGAAATTCACCGTGATAATGGAATCCTGGCAACCTTATCTCATGAGGCAGGAGGTGGGGAAGGTGCTTCTGCACAACCTCTGATCCCAAGGACTCCTCTCCCAGACTGTGACCTTAGACCATACCTCTCACCCCCCAATGCCTCGACTCCCCCAAAATCACAAAGAAGACCCTAGACCTATAATTTGTCTTCAGGTAGTAAATTCCCAATAGGTCTGCTGGAGTGGGCGCTGAGGGCTCCCTGCTGCTCAGACCTGAGCCCTCCAGGCAGCAGGGTCCCACTTACCCCCTCCCCACCCTGTTCCCCAAAGGTGGGAAAGAGGGGATTCCCCAGCCCAAGGCAGGGTTTTCCCAGCACCCTCCTGTAAGCAGAAGTCTCAGGGTCCAGACCCTTCCCTGAGCCCCCACCCCCACCCCAATTCCTGCCTACCAAGCAAGCAGCCCCAGCCTAGGGTCAGACAGGGTGAGCCTCATACAGACTGTGCCTTGATGGCCCCAGCCTTGGGAGAAGAATTTACTGTTAACCTGGAAGACTACTGAATCATTTTACCCTTGCCCAGTGGAATAGGACCTAAACATCCCCCTTCCGGGGAAAGTGGGTCATCTGAATTGGGGGTAGCAATTGATACTGTTTTGTAAACTACATTTCCTACAAAATATGAATTTATACTTTGA (SEQ ID NO: 41)>NP_001036189.1 nectin-2 isoform delta precursor [Homo sapiens]MARAAALLPSRSPPTPLLWPLLLLLLLETGAQDVRVQVLPEVRGQLGGTVELPCHLLPPVPGLYISLVTWQRPDAPANHQNVAAFHPKMGPSFPSPKPGSERLSFVSAKQSTGQDTEAELQDATLALHGLTVEDEGNYTCEFATFPKGSVRGMTWLRVIAKPKNQAEAQKVTFSQDPTTVALCISKEGRPPARISWLSSLDWEAKETQVSGTLAGTVTVTSRFTLVPSGRADGVTVTCKVEHESFEEPALIPVTLSVRYPPEVSISGYDDNWYLGRTDATLSCDVRSNPEPTGYDWSTTSGTFPTSAVAQGSQLVIHAVDSLFNTTFVCTVTNAVGMGRAEQVIFVRETPNTAGAGATGGIIGGIIAAIIATAVAATGILICRQQRKEQTLQGAEEDEDLEGPPSYKPPTPKAKLEAQEMPSQLFTLGASEHSPLKTPYFDAGASCTEQEMPRYHELPTLEERSGPLHPGATSLGSPIPVPPGPPAVEDVSLDLEDEEGEEEEEYLDKINPIYDALSYSSPSDSYQGKGFVMSRAMYV (SEQ ID NO: 42) Mouse Nectin->NM_008990.3 Mus musculus nectin cell adhesion molecule 2 2 (CD112)(Nectin2), transcript variant 1, mRNA isoform betaGAGCCCTAGGATCGGCTTGGCGAAGAGGGGCGGGGCCTGTGACGTCATGAGTCCGGCCCGCTGGAGCTAAGCGAGGGGCCGGGGGGCGCGGATCCTGAGAGCCAGGCGAGGGAAAGCTGGGCCGAACGAACTGATCCGGGGAGCCGTGAGCGGCGGAAGCCGGCCTGGAGCCGGACACTTCAGACCCCTGACTGCCCTCCCAGCCGATCGGTACACGAAGAGTGGTCCCTAGGCACCCCCTGCCCGGGCCCAGTCCCTCCCCGGGCCCCCCATGGCCCGGGCCGCAGTCCTCCCGCCGTCCAGATTGTCACCGACGCTGCCGTTGTTGCCGCTGCTACTGCTCCTGCTTCAGGAAACAGGAGCCCAAGATGTGCGGGTACGAGTGCTTCCCGAGGTCCGGGGCCGCTTGGGAGGCACCGTGGAGTTACCGTGCCACCTGCTCCCACCCACGACGGAGCGCGTCTCTCAGGTGACCTGGCAGCGCCTGGATGGCACAGTTGTGGCTGCTTTCCACCCATCCTTCGGAGTGGATTTCCCCAACTCTCAGTTCAGCAAGGACCGTCTGTCCTTTGTCAGAGCGAGACCAGAAACAAACGCAGACCTGCGGGATGCCACACTGGCCTTCCGGGGACTGAGGGTAGAGGACGAGGGCAATTACACCTGCGAGTTTGCCACGTTTCCCAACGGTACCCGCAGGGGGGTGACCTGGCTCAGAGTCATAGCCCAGCCTGAGAACCACGCTGAAGCCCAGGAGGTCACAATTGGCCCCCAGTCGGTGGCTGTAGCCCGCTGTGTCTCCACTGGGGGCCGCCCCCCTGCCCGAATCACCTGGATCTCATCTCTGGGTGGAGAGGCCAAAGATACTCAGGAGCCAGGGATACAGGCTGGCACCGTCACTATCATCAGCCGATACTCCTTGGTGCCCGTGGGCCGAGCGGATGGCGTCAAGGTCACGTGTAGAGTGGAACACGAGAGCTTCGAAGAGCCGATCCTGCTGCCAGTGACCCTCTCTGTGCGCTACCCTCCAGAAGTATCCATCTCCGGCTATGATGACAACTGGTACCTTGGCCGCAGTGAGGCCATACTGACCTGTGATGTACGAAGCAACCCAGAGCCCACAGACTATGACTGGAGCACGACCTCGGGCGTCTTCCCAGCCTCTGCAGTGGCCCAGGGCTCTCAGCTGCTTGTCCACTCTGTGGATCGAATGGTCAACACTACCTTCATCTGTACAGCCACCAACGCTGTGGGGACAGGCCGTGCTGAGCAGGTCATCCTGGTGCGAGAGTCACCCAGCACAGCAGGAGCAGGGGCCACTGGTGGCATCATTGGAGGTATTATCGCTGCCATCATCGCCACCGCAGTGGCTGGCACAGGCATCCTCATCTGCCGACAACAGCGGAAGGAGCAGAGGCTTCAAGCTGCGGATGAGGAAGAAGAACTGGAAGGACCTCCCTCCTATAAACCACCCACCCCGAAGGCCAAGCTGGAGGAACCAGAGATGCCCTCTCAACTCTTCACCTTGGGGGCCTCAGAGCACAGCCCAGTGAAGACGCCATACTTTGATGCTGGTGTCTCTTGTGCTGATCAGGAGATGCCTCGGTATCACGAGCTGCCCACTCTGGAAGAGCGGTCAGGGCCCCTGCTGTTGGGGGCTACAGGCCTGGGACCTTCTCTTCTGGTGCCTCCAGGACCCAATGTTGTGGAGGGGGTTTCCCTGAGTCTCGAAGATGAGGAGGAAGATGATGAGGAGGAAGACTTCCTGGATAAAATCAACCCTATTTATGATGCCCTGTCCTACCCCAGCCCCTCTGACTCCTACCAGAGCAAAGACTTTTTTGTGTCACGGGCCATGTATGTGTGAGGGAGGCACAGGGGCTCTGACGTCTCACCTTTCACCCTTGACCCATGAGCTTTCCACCAGTAATCTAGGACACTCTGACTTCCAGGCAGACCAGGGACAACTATCACCCATTGCAATCCACCTGTGACTTCTTAGTGACTCCACCATGACGTCCAATCTATGATGTCTGAGGCAGGCAAACCTGCACAACTGGAAACCTGGAGATTTTTATCTCCCTTGGCAGGGAGCTCACCATATCCTTCTGCACCACCTGTGACCCCCCCCCCCCCCCCAAGGACTCCTAAGACTACGACCCTTTGACCATGCCACTCAGTATCTCAAGAACCCTTAAAGTCCCAAAGGAATCGGACCTTGCACTTGTCCTCAGGCAATAGAGTCCAACAGATATGCAAGAACGGGATCAGGGGCTCCCTGTTGCTCAGACCTGAGCCCTCCAGGCAGCAGAAGCTCACCTGATCCCTCCCCACCCTGCTCCCCAAAGGTGAAAAGGAGAGGATTCCCCAATGTAAGGTAGGACCTCCCCATCTCCACCTACTCCTGCAGGCAGGAATCTCAGGTTTCTCACACCCTCTCCTCAGCACCCAGGTTCCTGTCTCCAGAGCATGAATTCCAGGTCCAATGCTAGAGGGGAGAACCTAATGCAAGTGTGCCTTGCCACCCCAAGTTTGGGAGACTCTGCTCTTATCCTGAGGACTACTGAATTCTTTTAACCCCTACCCAGTGAGATGAGAACTACATATCCCTCTTTAGGGGATGGTGTGTGTATGTGTGTGTGATGGAGAATCTGGGCATCTGGGTTGGGAATTTTATTTTGTAAGCATTTCCTACATAATATGAGTTTCTACTTTGATAAAGTCTTGTGTTTTCTGTG (SEQ ID NO: 43)>NP_033016.3 nectin-2 isoform 1 precursor [Mus musculus]MARAAVLPPSRLSPTLPLLPLLLLLLQETGAQDVRVRVLPEVRGRLGGTVELPCHLLPPTTERVSQVTWQRLDGTVVAAFHPSFGVDFPNSQFSKDRLSFVRARPETNADLRDATLAFRGLRVEDEGNYTCEFATFPNGTRRGVTWLRVIAQPENHAEAQEVTIGPQSVAVARCVSTGGRPPARITWISSLGGEAKDTQEPGIQAGTVTIISRYSLVPVGRADGVKVTCRVEHESFEEPILLPVTLSVRYPPEVSISGYDDNWYLGRSEAILTCDVRSNPEPTDYDWSTTSGVFPASAVAQGSQLLVHSVDRMVNTTFICTATNAVGTGRAEQVILVRESPSTAGAGATGGIIGGIIAAIIATAVAGTGILICRQQRKEQRLQAADEEEELEGPPSYKPPTPKAKLEEPEMPSQLFTLGASEHSPVKTPYFDAGVSCADQEMPRYHELPTLEERSGPLLLGATGLGPSLLVPPGPNVVEGVSLSLEDEEEDDEEEDFLDKINPIYDALSYPSPSDSYQSKDFFVSRAMYV (SEQ ID NO: 44) Human IL-10>NM_000572.3 Homo sapiens interleukin 10 (IL10),transcript variant 1, mRNAACACATCAGGGGCTTGCTCTTGCAAAACCAAACCACAAGACAGACTTGCAAAAGAAGGCATGCACAGCTCAGCACTGCTCTGTTGCCTGGTCCTCCTGACTGGGGTGAGGGCCAGCCCAGGCCAGGGCACCCAGTCTGAGAACAGCTGCACCCACTTCCCAGGCAACCTGCCTAACATGCTTCGAGATCTCCGAGATGCCTTCAGCAGAGTGAAGACTTTCTTTCAAATGAAGGATCAGCTGGACAACTTGTTGTTAAAGGAGTCCTTGCTGGAGGACTTTAAGGGTTACCTGGGTTGCCAAGCCTTGTCTGAGATGATCCAGTTTTACCTGGAGGAGGTGATGCCCCAAGCTGAGAACCAAGACCCAGACATCAAGGCGCATGTGAACTCCCTGGGGGAGAACCTGAAGACCCTCAGGCTGAGGCTACGGCGCTGTCATCGATTTCTTCCCTGTGAAAACAAGAGCAAGGCCGTGGAGCAGGTGAAGAATGCCTTTAATAAGCTCCAAGAGAAAGGCATCTACAAAGCCATGAGTGAGTTTGACATCTTCATCAACTACATAGAAGCCTACATGACAATGAAGATACGAAACTGAGACATCAGGGTGGCGACTCTATAGACTCTAGGACATAAATTAGAGGTCTCCAAAATCGGATCTGGGGCTCTGGGATAGCTGACCCAGCCCCTTGAGAAACCTTATTGTACCTCTCTTATAGAATATTTATTACCTCTGATACCTCAACCCCCATTTCTATTTATTTACTGAGCTTCTCTGTGAACGATTTAGAAAGAAGCCCAATATTATAATTTTTTTCAATATTTATTATTTTCACCTGTTTTTAAGCTGTTTCCATAGGGTGACACACTATGGTATTTGAGTGTTTTAAGATAAATTATAAGTTACATAAGGGAGGAAAAAAAATGTTCTTTGGGGAGCCAACAGAAGCTTCCATTCCAAGCCTGACCACGCTTTCTAGCTGTTGAGCTGTTTTCCCTGACCTCCCTCTAATTTATCTTGTCTCTGGGCTTGGGGCTTCCTAACTGCTACAAATACTCTTAGGAAGAGAAACCAGGGAGCCCCTTTGATGATTAATTCACCTTCCAGTGTCTCGGAGGGATTCCCCTAACCTCATTCCCCAACCACTTCATTCTTGAAAGCTGTGGCCAGCTTGTTATTTATAACAACCTAAATTTGGTTCTAGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCTGAGGCGGGTGGATCACTTGAGGTCAGGAGTTCCTAACCAGCCTGGTCAACATGGTGAAACCCCGTCTCTACTAAAAATACAAAAATTAGCCGGGCATGGTGGCGCGCACCTGTAATCCCAGCTACTTGGGAGGCTGAGGCAAGAGAATTGCTTGAACCCAGGAGATGGAAGTTGCAGTGAGCTGATATCATGCCCCTGTACTCCAGCCTGGGTGACAGAGCAAGACTCTGTCTCAAAAAATAAAAATAAAAATAAATTTGGTTCTAATAGAACTCAGTTTTAACTAGAATTTATTCAATTCCTCTGGGAATGTTACATTGTTTGTCTGTCTTCATAGCAGATTTTAATTTTGAATAAATAAATGTATCTTATTCACATCA (SEQ ID NO: 45)>NP_000563.1 inter1eukin-10 isoform 1 precursor [Homo sapiens]MHSSALLCCLVLLTGVRASPGQGTQSENSCTHFPGNLPNMLRDLRDAFSRVKTFFQMKDQLDNLLLKESLLEDFKGYLGCQALSEMIQFYLEEVMPQAENQDPDIKAHVNSLGENLKTLRLRLRRCHRFLPCENKSKAVEQVKNAFNKLQEKGIYKAMSEFDIFINYIEAYMTMKIRN (SEQ ID NO: 46) Mouse IL-10>NM_010548.2 Mus musculus interleukin 10 (Il10), mRNAACATTTAGAGACTTGCTCTTGCACTACCAAAGCCACAAGGCAGCCTTGCAGAAAAGAGAGCTCCATCATGCCTGGCTCAGCACTGCTATGCTGCCTGCTCTTACTGACTGGCATGAGGATCAGCAGGGGCCAGTACAGCCGGGAAGACAATAACTGCACCCACTTCCCAGTCGGCCAGAGCCACATGCTCCTAGAGCTGCGGACTGCCTTCAGCCAGGTGAAGACTTTCTTTCAAACAAAGGACCAGCTGGACAACATACTGCTAACCGACTCCTTAATGCAGGACTTTAAGGGTTACTTGGGTTGCCAAGCCTTATCGGAAATGATCCAGTTTTACCTGGTAGAAGTGATGCCCCAGGCAGAGAAGCATGGCCCAGAAATCAAGGAGCATTTGAATTCCCTGGGTGAGAAGCTGAAGACCCTCAGGATGCGGCTGAGGCGCTGTCATCGATTTCTCCCCTGTGAAAATAAGAGCAAGGCAGTGGAGCAGGTGAAGAGTGATTTTAATAAGCTCCAAGACCAAGGTGTCTACAAGGCCATGAATGAATTTGACATCTTCATCAACTGCATAGAAGCATACATGATGATCAAAATGAAAAGCTAAAACACCTGCAGTGTGTATTGAGTCTGCTGGACTCCAGGACCTAGACAGAGCTCTCTAAATCTGATCCAGGGATCTTAGCTAACGGAAACAACTCCTTGGAAAACCTCGTTTGTACCTCTCTCCGAAATATTTATTACCTCTGATACCTCAGTTCCCATTCTATTTATTCACTGAGCTTCTCTGTGAACTATTTAGAAAGAAGCCCAATATTATAATTTTACAGTATTTATTATTTTTAACCTGTGTTTAAGCTGTTTCCATTGGGGACACTTTATAGTATTTAAAGGGAGATTATATTATATGATGGGAGGGGTTCTTCCTTGGGAAGCAATTGAAGCTTCTATTCTAAGGCTGGCCACACTTGAGAGCTGCAGGGCCCTTTGCTATGGTGTCCTTTCAATTGCTCTCATCCCTGAGTTCAGAGCTCCTAAGAGAGTTGTGAAGAAACTCATGGGTCTTGGGAAGAGAAACCAGGGAGATCCTTTGATGATCATTCCTGCAGCAGCTCAGAGGGTTCCCCTACTGTCATCCCCCAGCCGCTTCATCCCTGAAAACTGTGGCCAGTTTGTTATTTATAACCACCTAAAATTAGTTCTAATAGAACTCATTTTTAACTAGAAGTAATGCAATTCCTCTGGGAATGGTGTATTGTTTGTCTGCCTTTGTAGCAGACTCTAATTTTGAATAAATGGATCTTATTCG (SEQ ID NO: 47)>NP_034678.1 inter1eukin-10 precursor [Mus musculus]MPGSALLCCLLLLTGMRISRGQYSREDNNCTHFPVGQSHMLLELRTAFSQVKTFFQTKDQLDNILLTDSLMQDFKGYLGCQALSEMIQFYLVEVMPQAEKHGPEIKEHLNSLGEKLKTLRMRLRRCHRFLPCENKSKAVEQVKSDFNKLQDQGVYKAMNEFDIFINCIEAYMMIKMKS (SEQ ID NO: 48) Human TSG-6>NM_007115.3 Homo sapiens TNF alpha induced protein 6 (TNFAIP6), mRNAAGTCACATTTCAGCCACTGCTCTGAGAATTTGTGAGCAGCCCCTAACAGGCTGTTACTTCACTACAACTGACGATATGATCATCTTAATTTACTTATTTCTCTTGCTATGGGAAGACACTCAAGGATGGGGATTCAAGGATGGAATTTTTCATAACTCCATATGGCTTGAACGAGCAGCCGGTGTGTACCACAGAGAAGCACGGTCTGGCAAATACAAGCTCACCTACGCAGAAGCTAAGGCGGTGTGTGAATTTGAAGGCGGCCATCTCGCAACTTACAAGCAGCTAGAGGCAGCCAGAAAAATTGGATTTCATGTCTGTGCTGCTGGATGGATGGCTAAGGGCAGAGTTGGATACCCCATTGTGAAGCCAGGGCCCAACTGTGGATTTGGAAAAACTGGCATTATTGATTATGGAATCCGTCTCAATAGGAGTGAAAGATGGGATGCCTATTGCTACAACCCACACGCAAAGGAGTGTGGTGGCGTCTTTACAGATCCAAAGCAAATTTTTAAATCTCCAGGCTTCCCAAATGAGTACGAAGATAACCAAATCTGCTACTGGCACATTAGACTCAAGTATGGTCAGCGTATTCACCTGAGTTTTTTAGATTTTGACCTTGAAGATGACCCAGGTTGCTTGGCTGATTATGTTGAAATATATGACAGTTACGATGATGTCCATGGCTTTGTGGGAAGATACTGTGGAGATGAGCTTCCAGATGACATCATCAGTACAGGAAATGTCATGACCTTGAAGTTTCTAAGTGATGCTTCAGTGACAGCTGGAGGTTTCCAAATCAAATATGTTGCAATGGATCCTGTATCCAAATCCAGTCAAGGAAAAAATACAAGTACTACTTCTACTGGAAATAAAAACTTTTTAGCTGGAAGATTTAGCCACTTATAAAAAAAAAAAAAAGGATGATCAAAACACACAGTGTTTATGTTGGAATCTTTTGGAACTCCTTTGATCTCACTGTTATTATTAACATTTATTTATTATTTTTCTAAATGTGAAAGCAATACATAATTTAGGGAAAATTGGAAAATATAGGAAACTTTAAACGAGAAAATGAAACCTCTCATAATCCCACTGCATAGAAATAACAAGCGTTAACATTTTCATATTTTTTTCTTTCAGTCATTTTTCTATTTGTGGTATATGTATATATGTACCTATATGTATTTGCATTTGAAATTTTGGAATCCTGCTCTATGTACAGTTTTGTATTATACTTTTTAAATCTTGAACTTTATAAACATTTTCTGAAATCATTGATTATTCTACAAAAACATGATTTTAAACAGCTGTAAAATATTCTATGATATGAATGTTTTATGCATTATTTAAGCCTGTCTCTATTGTTGGAATTTCAGGTCATTTTCATAAATATTGTTGCAATAAATATCCTTGAACACACAAAAAAAAAAAAAAAA (SEQ ID NO: 49) >NP_009046.2 tumor necrosis factor-inducible gene 6protein precursor [Homo sapiens]MIILIYLFLLLWEDTQGWGFKDGIFHNSIWLERAAGVYHREARSGKYKLTYAEAKAVCEFEGGHLATYKQLEAARKIGFHVCAAGWMAKGRVGYPIVKPGPNCGFGKTGIIDYGIRLNRSERWDAYCYNPHAKECGGVFTDPKQIFKSPGFPNEYEDNQICYWHIRLKYGQRIHLSFLDFDLEDDPGCLADYVEIYDSYDDVHGFVGRYCGDELPDDIISTGNVMTLKFLSDASVTAGGFQIKYVAMDPVSKSSQGKNTSTTSTGNKNFLAGRFSHL (SEQ ID NO: 50)Mouse TSG-6 >NM_009398.2 Mus musculus tumor necrosis factor alphainduced protein 6 (Tnfaip6), mRNACCGCTGCTCTGAGAATTTCGTGTGGGCAGCCCCGACATTGTAACCGGCTCTGCAACCGAAGAGATGGTCGTCCTCCTTTGCTTATGCGTCTTGCTGTGGGAAGAGGCTCACGGATGGGGATTCAAGAACGGGATCTTTCATAACTCCATATGGCTTGAACAAGCAGCGGGCGTATACCACAGAGAAGCTCGGGCTGGCAGATACAAGCTCACCTACGCCGAAGCCAAGGCCGTATGTGAATTTGAAGGTGGTCGTCTCGCAACCTACAAGCAGCTAGAGGCAGCCAGAAAAATTGGATTCCATGTCTGTGCTGCTGGATGGATGGCCAAGGGTAGAGTCGGATACCCCATTGTGAAACCTGGGCCCAACTGTGGATTTGGGAAAACGGGTATCATCGATTATGGAATCCGGCTCAACAGGAGTGAGCGATGGGATGCCTATTGCTACAACCCACATGCAAAGGAGTGTGGTGGTGTCTTCACAGATCCGAAGCGAATTTTTAAATCCCCGGGCTTCCCAAATGAGTACGATGACAACCAGGTCTGCTACTGGCACATTCGGCTCAAGTACGGTCAGCGAATTCACCTGAGCTTTTTGGACTTTGACCTTGAACATGATCCAGGCTGCTTGGCTGACTATGTAGAAATCTATGACAGTTATGATGACGTCCACGGCTTTGTAGGAAGATACTGTGGTGATGAACTTCCAGAAGACATCATTAGCACAGGAAATGTCATGACCTTGAAGTTTCTGAGTGATGCATCCGTCACGGCTGGAGGCTTCCAGATTAAATACGTCACAGTGGATCCTGCATCTAAATCCAGTCAAGCCAAAAATACAAGTACTACTGGAAATAAGAAGTTCTTACCTGGAAGGTTTAGCCATCTATAAAAAATTTTTTTTAAAAATGTTCAAAACATCCAGTACAATATTTATATTTGTTTTTGTTGTTGTTGTTGGTTTTTTTTTTTTTATTTTGTTTTGTTTTGTTTTTTTGAGACGGGGTTTCTCTGTATAGCCTTGGCTGTCCTGGAACTCACTTTGAAGACCAGGCTGGCCTCGAACTCAGAAATCCACCTGCCTCCGCCTACCAAGTGCTGGGATTAAAGGCGTCCACCACCACCGCCCGGCTTCAATATTTATATTTGTAGCTCTTGGACCTCGTTTGTTCTCTTTTGTATTTTTATTATTAACATGTATTTATTATTTTTCCAAATGTGAAAGCCATATGTAATTATGTGGAAAATTGACAAATAAATACAGAGAACTTCAAATGAGTTTTTTTTTTAAATCTCATAATTGTACTACACAGAAATAACTAATGTTAAAGTTTTTAAATGTTTGTCTTTCATTCATTTTTCTACTTGTAGTATATGTACATATGTAACTCTATGATTTGCGTTTGAATTTTGGCATTCTGCCTTTTGTAACCTGATATTTTTAACCTTGACATTGTATAGCTCAAGCACTTCCCAAGATCTCTGAGTTTTCTACAAAATGGGACTTTGTAAATATGATTGTTCCCTGCTTTATTTAAGCTGAATTTATATTAGGATTTAAGGTTGTTTTCATAAATATTGCTGTAATAAATACTTTTGGAT (SEQ ID NO: 51) >NP_033424.1 tumor necrosis factor-inducible gene 6protein precursor [Mus musculus]MVVLLCLCVLLWEEAHGWGFKNGIFHNSIWLEQAAGVYHREARAGRYKLTYAEAKAVCEFEGGRLATYKQLEAARKIGFHVCAAGWMAKGRVGYPIVKPGPNCGFGKTGIIDYGIRLNRSERWDAYCYNPHAKECGGVFTDPKRIFKSPGFPNEYDDNQVCYWHIRLKYGQRIHLSFLDFDLEHDPGCLADYVEIYDSYDDVHGFVGRYCGDELPEDIISTGNVMTLKFLSDASVTAGGFQIKYVTVDPASKSSQAKNTSTTGNKKFLPGRFSHL (SEQ ID NO: 52)Human B7-H3  >NM_001024736.2 Homo sapiens CD276 molecule (CD276),(CD276) transcript variant 1, mRNAATTCGGGCCGGGCCTCGCTGCGGCGGCGACTGAGCCAGGCTGGGCCGCGTCCCTGAGTCCCAGAGTCGGCGCGGCGCGGCAGGGGCAGCCTTCCACCACGGGGAGCCCAGCTGTCAGCCGCCTCACAGGAAGATGCTGCGTCGGCGGGGCAGCCCTGGCATGGGTGTGCATGTGGGTGCAGCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTGGAGGTCCAGGTCCCTGAAGACCCAGTGGTGGCACTGGTGGGCACCGATGCCACCCTGTGCTGCTCCTTCTCCCCTGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGCTGACAGATACCAAACAGCTGGTGCACAGCTTTGCTGAGGGCCAGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGGCACAGGGCAACGCATCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCAGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGCACAGCATCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACAGCTCTGTCACCATCACACCCCAGAGAAGCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCCCTAGTGGGCACCGATGCCACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGCACAGCGTCCTGCGGGTGGTGCTGGGTGCGAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACGGCTCTGTCACCATCACAGGGCAGCCTATGACATTCCCCCCAGAGGCCCTGTGGGTGACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGTGGCCCTGGCTTTCGTGTGCTGGAGAAAGATCAAACAGAGCTGTGAGGAGGAGAATGCAGGAGCTGAGGACCAGGATGGGGAGGGAGAAGGCTCCAAGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAAGAAGATGATGGACAAGAAATAGCCTGACCATGAGGACCAGGGAGCTGCTACCCCTCCCTACAGCTCCTACCCTCTGGCTGCAATGGGGCTGCACTGTGAGCCCTGCCCCCAACAGATGCATCCTGCTCTGACAGGTGGGCTCCTTCTCCAAAGGATGCGATACACAGACCACTGTGCAGCCTTATTTCTCCAATGGACATGATTCCCAAGTCATCCTGCTGCCTTTTTTCTTATAGACACAATGAACAGACCACCCACAACCTTAGTTCTCTAAGTCATCCTGCCTGCTGCCTTATTTCACAGTACATACATTTCTTAGGGACACAGTACACTGACCACATCACCACCCTCTTCTTCCAGTGCTGCGTGGACCATCTGGCTGCCTTTTTTCTCCAAAAGATGCAATATTCAGACTGACTGACCCCCTGCCTTATTTCACCAAAGACACGATGCATAGTCACCCCGGCCTTGTTTCTCCAATGGCCGTGATACACTAGTGATCATGTTCAGCCCTGCTTCCACCTGCATAGAATCTTTTCTTCTCAGACAGGGACAGTGCGGCCTCAACATCTCCTGGAGTCTAGAAGCTGTTTCCTTTCCCCTCCTTCCTCCTCTTGCTCTAGCCTTAATACTGGCCTTTTCCCTCCCTGCCCCAAGTGAAGACAGGGCACTCTGCGCCCACCACATGCACAGCTGTGCATGGAGACCTGCAGGTGCACGTGCTGGAACACGTGTGGTTCCCCCCTGGCCCAGCCTCCTCTGCAGTGCCCCTCTCCCCTGCCCATCCTCCCCACGGAAGCATGTGCTGGTCACACTGGTTCTCCAGGGGTCTGTGATGGGGCCCCTGGGGGTCAGCTTCTGTCCCTCTGCCTTCTCACCTCTTTGTTCCTTTCTTTTCATGTATCCATTCAGTTGATGTTTATTGAGCAACTACAGATGTCAGCACTGTGTTAGGTGCTGGGGGCCCTGCGTGGGAAGATAAAGTTCCTCCCTCAAGGACTCCCCATCCAGCTGGGAGACAGACAACTAACTACACTGCACCCTGCGGTTTGCAGGGGGCTCCTGCCTGGCTCCCTGCTCCACACCTCCTCTGTGGCTCAAGGCTTCCTGGATACCTCACCCCCATCCCACCCATAATTCTTACCCAGAGCATGGGGTTGGGGCGGAAACCTGGAGAGAGGGACATAGCCCCTCGCCACGGCTAGAGAATCTGGTGGTGTCCAAAATGTCTGTCCAGGTGTGGGCAGGTGGGCAGGCACCAAGGCCCTCTGGACCTTTCATAGCAGCAGAAAAGGCAGAGCCTGGGGCAGGGCAGGGCCAGGAATGCTTTGGGGACACCGAGGGGACTGCCCCCCACCCCCACCATGGTGCTATTCTGGGGCTGGGGCAGTCTTTTCCTGGCTTGCCTCTGGCCAGCTCCTGGCCTCTGGTAGAGTGAGACTTCAGACGTTCTGATGCCTTCCGGATGTCATCTCTCCCTGCCCCAGGAATGGAAGATGTGAGGACTTCTAATTTAAATGTGGGACTCGGAGGGATTTTGTAAACTGGGGGTATATTTTGGGGAAAATAAATGTCTTTGTAAAAA (SEQ ID NO: 53)>NP_001019907.1 CD276 antigen isoform a precursor [Homo sapiens]MLRRRGSPGMGVHVGAALGALWFCLTGALEVQVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANGTYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVCWRKIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA (SEQ ID NO: 54) Mouse B7-H3>NM_133983.4 Mus musculus CD276 antigen (Cd276), mRNA (CD276)CGGCGCGGCGCGCCAAAGTGACCTGGTACAGCCTGGACCCCAAGCTCATCGGCTTTGTCTGGCTGGCCGCCTGGCCTCTTCCCACTTGGATTTGGATGATCCTGAGGCCTTTGGAGGAACTTCGAGACAAAGGCCCCTCTTCCTCTTCCACGGGCAGGAGCAGCCATTCGCCACGGAGAGCCCAGCTGTCAGCTGTCTCACAGGAAGATGCTTCGAGGATGGGGTGGCCCCAGTGTGGGTGTGTGTGTGCGCACAGCACTGGGGGTGCTGTGCCTCTGCCTCACAGGAGCTGTGGAAGTCCAGGTCTCTGAAGACCCCGTGGTGGCCCTGGTGGACACGGATGCCACCCTACGCTGCTCCTTTTCCCCAGAGCCTGGCTTCAGTCTGGCACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGCTTCACGGAGGGCCGGGACCAAGGCAGTGCCTACTCCAACCGCACAGCGCTCTTCCCTGACCTGTTGGTGCAAGGCAATGCGTCCTTGAGGCTGCAGCGCGTCCGAGTAACCGACGAGGGCAGCTACACCTGCTTTGTGAGCATCCAGGACTTTGACAGCGCTGCTGTTAGCCTGCAGGTGGCCGCCCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTACGTCCAGGGAACATGGTGACCATCACGTGCTCTAGCTACCAGGGCTATCCGGAGGCCGAGGTGTTCTGGAAGGATGGACAGGGAGTGCCCTTGACTGGCAATGTGACCACATCCCAGATGGCCAACGAGCGGGGCTTGTTCGATGTTCACAGCGTGCTGAGGGTGGTGCTGGGTGCTAACGGCACCTACAGCTGCCTGGTACGCAACCCGGTGTTGCAGCAAGATGCTCACGGCTCAGTCACCATCACAGGGCAGCCCCTGACATTCCCCCCTGAGGCTCTGTGGGTAACCGTGGGGCTCTCTGTCTGTCTTGTGGTACTACTGGTGGCCCTGGCTTTCGTGTGCTGGAGAAAGATCAAGCAGAGCTGCGAGGAGGAGAATGCAGGTGCCGAGGACCAGGATGGAGATGGAGAAGGATCCAAGACAGCTCTACGGCCTCTGAAACCCTCTGAAAACAAAGAAGATGACGGACAAGAAATTGCTTGATTGGGAGCTGCTGCCCTTCCCAGGTGGGGGGCCCACCCTCTGGCAGTGTTGAGCTTCAATGCGAGCCCTTCCCCCAACGAATGGGTTTGTCCCACAGATCTACCCGTTCGTCAAAGGACGTGGTCCATAGACCACCCACAGCCTTACTTTTCCAATGGACTTAATTCCCATCATCCTGCAGCCTCATTTCTCCAGTGACACGATACACGAACCATCCTGCGGCCTTATTTCCCACGGACACGACACAAAGATGTCCCTCCTCGGTGTTCCTCCAGAGTCGTCTGGTGGCCTTGTGATACGGCGTGAACCTTCTTCCTTCTGCCTTACGTCTAATGGACACACACGCACCACCCCCACACCCTTGCTCCTCCAAAGCCATGCAGACTGTGTAACTGCTATTATTCTCCAAGGGGCATCCTGTGCAGATGAAACCCTGCTTTATTTCCCTGAAGACAGCTGCACAGTGACCTCTTAGTTCTTGCTCCCATGGCCCTGATGTATCCTAGTTACCAGCCCTCAACCTCAGTTCTGAGGGTGGGATCCCATCGCTCAGCAAGGCTTCATCCTGACCTCCCTGCCCTGATCTGATCTGGCCCTGGCTTTTGTTGTCTCGCTCCCTGACTAAGTGAGATGGGGCACTCTCCCGCCCCCGCCCCCCCCAGGTCACAGATACCTACCTGCAGCTGTGCGTGCTGGATCACGCACATACTTGCCTTGCATGGTCTCCTGGCTGCCCTGGGCTGTGCCTGTTCTTCCATAGGAAGCAAGTTCTTGTCTCCCTGGTTCTCAGGGCCCCTCAGGGGCTCAGCCTTCAGCCCTGTGCTTCCCCATGTTGGGAATCTTTGTTACCTTTTTCTTCTTTGTAAATTAACATCTGATAACAACCACAGGGTCCAATGGGACTTTCACAGACCTGCCAGCTAGATAAATAATGACAACAGAAGTTTATTAATATTTTAAGACTTAGGCCTTTTGCTGGGCAGCCTCCCAACTATTCTATCCTGACTAATCCTGGCACTATGTCCCACCACATGGCCAGGTCTACCTCTCTGCTCCACTCTCCATCCACCTCCATGTCTGCCAGCAAATCTCCCGTGATTCAGTTCTTCTCCCAGAGTCCCTATCTCTGCCCAGAAGTACCATCTTCGACTTCCTGCCCAACTATTGGCCGTCAGCTCTTCATTAAAGCCGATCAGATGTAATTCTAGATTGCCTTAGGCAGGTGAGGAAGAAACAAGTATTTGTAAAATATGAGACCAGCAATGGGCCATAGAAATAACAGCACCAGATCCTGCCAGCATTTAGCCCTCTGTTGGTACAAAATTAACAATTGAATATACAGAGACCTACTTCCAGAGTGTACCCCAACAACAGGCGTGAGCATGGTGCTGGGTACTAGGGTCCTGCTGGAAAATCAGAGACCTTACCTACAGCTGGGACATGACCTTGCTTCCGACTTACCCACCACTTCTGGATACCTCACCCTCAGCCCACACTATCCCTGGCCTAGGGCCCAGGGTAGAGCCAGAAACATGGAGAAAGCATGGCCCCTTGCCGTACCTGGAGAACTGGGTATTTTCCAGAGTCTTTATAGATGTGGACTGGAAGGCAGGTGGCCACAGCCGTGCAGACCTGGGTCAGGTCAGAAACCTATGCCATGCTGGGACCTACTCAACAGCAGAAGCATGAAGAGGGCCTGAGGACAAGAAAGGCCTTCTTACCATGGTGCTATTCTGGAGCTGGGATATATACCTGGCTTGTCTCTGACTGCCCTGGCTTCTGGCAGAACTTCTGATGTCCTCCTGAAGGCCTCTCTCCCACCCCAGTACCTGAGAACCTGAGGATAATTTAAACATGGGACTCTGGCCAGCACCTGGGAGAGACAGGTAGATCTCTGATTTTTGACTCAGCCTGGTCTATCGAGTGAGTTCCAGGACATCTGGGGCTACACAGAGAAACCATCTTAAAGACTAAAAATAATAAACATGAGACTGTAAACTGGGTGTATTTTGGGAGAAATAAATGTCTTTTTCTTTCAA (SEQ ID NO: 55)>NP_598744.1 0D276 antigen precursor [Mus musculus]MLRGWGGPSVGVCVRTALGVLCLCLTGAVEVQVSEDPVVALVDTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEGRDQGSAYSNRTALFPDLLVQGNASLRLQRVRVTDEGSYTCFVSIQDFDSAAVSLQVAAPYSKPSMTLEPNKDLRPGNMVTITCSSYQGYPEAEVFWKDGQGVPLTGNVTTSQMANERGLFDVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPLTFPPEALWVTVGLSVCLVVLLVALAFVCWRKIKQSCEEENAGAEDQDGDGEGSKTALRPLKPSENKEDDGQEIA (SEQ ID NO: 56) Human B7-H4>NM_024626.4 Homo sapiens V-set domain containing T cell (VTCN1)activation inhibitor 1 (VTCN1), transcript variant 1, mRNAGTGAGTCACCAAGGAAGGCAGCGGCAGCTCCACTCAGCCAGTACCCAGATACGCTGGGAACCTTCCCCAGCCATGGCTTCCCTGGGGCAGATCCTCTTCTGGAGCATAATTAGCATCATCATTATTCTGGCTGGAGCAATTGCACTCATCATTGGCTTTGGTATTTCAGGGAGACACTCCATCACAGTCACTACTGTCGCCTCAGCTGGGAACATTGGGGAGGATGGAATCCTGAGCTGCACTTTTGAACCTGACATCAAACTTTCTGATATCGTGATACAATGGCTGAAGGAAGGTGTTTTAGGCTTGGTCCATGAGTTCAAAGAAGGCAAAGATGAGCTGTCGGAGCAGGATGAAATGTTCAGAGGCCGGACAGCAGTGTTTGCTGATCAAGTGATAGTTGGCAATGCCTCTTTGCGGCTGAAAAACGTGCAACTCACAGATGCTGGCACCTACAAATGTTATATCATCACTTCTAAAGGCAAGGGGAATGCTAACCTTGAGTATAAAACTGGAGCCTTCAGCATGCCGGAAGTGAATGTGGACTATAATGCCAGCTCAGAGACCTTGCGGTGTGAGGCTCCCCGATGGTTCCCCCAGCCCACAGTGGTCTGGGCATCCCAAGTTGACCAGGGAGCCAACTTCTCGGAAGTCTCCAATACCAGCTTTGAGCTGAACTCTGAGAATGTGACCATGAAGGTTGTGTCTGTGCTCTACAATGTTACGATCAACAACACATACTCCTGTATGATTGAAAATGACATTGCCAAAGCAACAGGGGATATCAAAGTGACAGAATCGGAGATCAAAAGGCGGAGTCACCTACAGCTGCTAAACTCAAAGGCTTCTCTGTGTGTCTCTTCTTTCTTTGCCATCAGCTGGGCACTTCTGCCTCTCAGCCCTTACCTGATGCTAAAATAATGTGCCTCGGCCACAAAAAAGCATGCAAAGTCATTGTTACAACAGGGATCTACAGAACTATTTCACCACCAGATATGACCTAGTTTTATATTTCTGGGAGGAAATGAATTCATATCTAGAAGTCTGGAGTGAGCAAACAAGAGCAAGAAACAAAAAGAAGCCAAAAGCAGAAGGCTCCAATATGAACAAGATAAATCTATCTTCAAAGACATATTAGAAGTTGGGAAAATAATTCATGTGAACTAGACAAGTGTGTTAAGAGTGATAAGTAAAATGCACGTGGAGACAAGTGCATCCCCAGATCTCAGGGACCTCCCCCTGCCTGTCACCTGGGGAGTGAGAGGACAGGATAGTGCATGTTCTTTGTCTCTGAATTTTTAGTTATATGTGCTGTAATGTTGCTCTGAGGAAGCCCCTGGAAAGTCTATCCCAACATATCCACATCTTATATTCCACAAATTAAGCTGTAGTATGTACCCTAAGACGCTGCTAATTGACTGCCACTTCGCAACTCAGGGGCGGCTGCATTTTAGTAATGGGTCAAATGATTCACTTTTTATGATGCTTCCAAAGGTGCCTTGGCTTCTCTTCCCAACTGACAAATGCCAAAGTTGAGAAAAATGATCATAATTTTAGCATAAACAGAGCAGTCGGCGACACCGATTTTATAAATAAACTGAGCACCTTCTTTTTAAACAAACAAATGCGGGTTTATTTCTCAGATGATGTTCATCCGTGAATGGTCCAGGGAAGGACCTTTCACCTTGTCTATATGGCATTATGTCATCACAAGCTCTGAGGCTTCTCCTTTCCATCCTGCGTGGACAGCTAAGACCTCAGTTTTCAATAGCATCTAGAGCAGTGGGACTCAGCTGGGGTGATTTCGCCCCCCATCTCCGGGGGAATGTCTGAAGACAATTTTGGTTACCTCAATGAGGGAGTGGAGGAGGATACAGTGCTACTACCAACTAGTGGATAGAGGCCAGGGATGCTGCTCAACCTCCTACCATGTACAGGACGTCTCCCCATTACAACTACCCAATCCGAAGTGTCAACTGTGTCAGGGCTAAGAAACCCTGGTTTTGAGTAGAAAAGGGCCTGGAAAGAGGGGAGCCAACAAATCTGTCTGCTTCCTCACATTAGTCATTGGCAAATAAGCATTCTGTCTCTTTGGCTGCTGCCTCAGCACAGAGAGCCAGAACTCTATCGGGCACCAGGATAACATCTCTCAGTGAACAGAGTTGACAAGGCCTATGGGAAATGCCTGATGGGATTATCTTCAGCTTGTTGAGCTTCTAAGTTTCTTTCCCTTCATTCTACCCTGCAAGCCAAGTTCTGTAAGAGAAATGCCTGAGTTCTAGCTCAGGTTTTCTTACTCTGAATTTAGATCTCCAGACCCTGCCTGGCCACAATTCAAATTAAGGCAACAAACATATACCTTCCATGAAGCACACACAGACTTTTGAAAGCAAGGACAATGACTGCTTGAATTGAGGCCTTGAGGAATGAAGCTTTGAAGGAAAAGAATACTTTGTTTCCAGCCCCCTTCCCACACTCTTCATGTGTTAACCACTGCCTTCCTGGACCTTGGAGCCACGGTGACTGTATTACATGTTGTTATAGAAAACTGATTTTAGAGTTCTGATCGTTCAAGAGAATGATTAAATATACATTTCCTACACCA (SEQ ID NO: 57) >NP_078902.2 V-set domain-containing T-cell activationinhibitor 1 isoform 1 precursor [Homo sapiens]MASLGQILFWSIISIIIILAGAIALIIGFGISGRHSITVTTVASAGNIGEDGILSCTFEPDIKLSDIVIQWLKEGVLGLVHEFKEGKDELSEQDEMFRGRTAVFADQVIVGNASLRLKNVQLTDAGTYKCYIITSKGKGNANLEYKTGAFSMPEVNVDYNASSETLRCEAPRWFPQPTVVWASQVDQGANFSEVSNTSFELNSENVTMKVVSVLYNVTINNTYSCMIENDIAKATGDIKVTESEIKRRSHLQLLNSKASLCVSSFFAISWALLPLSPYLMLK (SEQ ID NO: 58)Mouse B7-H4 >NM_178594.3 Mus musculus V-set domain containing T cell(VTCN1) activation inhibitor 1 (Vtcn1), mRNAGTGAGTCACAACACCCAGGAGGGCAGCAGCAGGCAGGCAGCTCCACTCACCAAAATCTGGCCCCACACACAGCAGGACTGTGGGAAGGAACTCCCTCTCCATGGCTTCCTTGGGGCAGATCATCTTTTGGAGTATTATTAACATCATCATCATCCTGGCTGGGGCCATCGCACTCATCATTGGCTTTGGCATTTCAGGCAAGCACTTCATCACGGTCACGACCTTCACCTCAGCTGGAAACATTGGAGAGGACGGGACCCTGAGCTGCACTTTTGAACCTGACATCAAACTCAACGGCATCGTCATCCAGTGGCTGAAAGAAGGCATCAAAGGTTTGGTCCACGAGTTCAAAGAAGGCAAAGACGACCTCTCACAGCAGCATGAGATGTTCAGAGGCCGCACAGCAGTGTTTGCTGATCAGGTGGTAGTTGGCAATGCTTCCCTGAGACTGAAAAACGTGCAGCTCACGGATGCTGGCACCTACACATGTTACATCCGCACCTCAAAAGGCAAAGGGAATGCAAACCTTGAGTATAAGACCGGAGCCTTCAGTATGCCAGAGATAAATGTGGACTATAATGCCAGTTCAGAGAGTTTACGCTGCGAGGCTCCTCGGTGGTTCCCCCAGCCCACAGTGGCCTGGGCATCTCAAGTCGACCAAGGAGCCAATTTCTCAGAAGTCTCCAACACCAGCTTTGAGTTGAACTCTGAGAATGTGACCATGAAGGTCGTATCTGTGCTCTACAATGTCACAATCAACAACACATACTCCTGTATGATTGAAAACGACATTGCCAAAGCCACCGGGGACATCAAAGTGACAGATTCAGAGGTCAAAAGGCGAAGTCAGCTGCAGTTGCTGAACTCTGGGCCTTCCCCGTGTGTTTTTTCTTCTGCCTTTGTGGCTGGCTGGGCACTCCTATCTCTCTCCTGTTGCCTGATGCTAAGATGAGGGGCCCTGGCTACACAAAAGCATGCAACGTTGCTGGTCCAACAGAATCCCGGAGAACTACAGAAATATTTTCCTCAAGACATGACCTAGTTTTATATTTCTAGAAGAAGATGAAATCATGTCTAGAAGTCTGGAGAGAGCAGACAGGAACAAGATGTGGAAGGAAAACAAAAGTAACCCACAGACACCCCCGATCGGAACAAGATGGACCTAGAAAATAATTCAACCAAACTAGAGTATACTAAGTGTGCTGTTACAATGTGTGTAGGGTAGGTGTCCTCCCACATCTCAGGGGCCTCCCCTGGTCCACCAGCTCCTGAGTTAGGATGGGCTGTTATGATGTCACTCTGAAGGTTCCTGGATGGTTCCTACTGCCATATACTCATTTTATATTCAGCACATTAAACCATAGTGAATGCTATGAAAAGCTGCTAATCAGCTGCCACTCCGAGATTCGGAGGTGGCAACGTCTGAGTGACAGGTCCAGTGATTCGCTTCTCCTTAGGATGCTTTTACAAGCTCTTTGGCGTCTCCTCCCACCTGGCAAATGCCAAATGCATAGGGGAGGGTGATCATCATTCTAGGGCAAACAAAATAGTTGAGGGATGCTGATTTCCCAAATCATCCGAATCACTTCTCCCTTGAGCAAACAAGCGCCCTGTTATTTCTCAAATGCTGCTTTGTGAATCAGTCCAGGGCAAGGCGCTCTCCTCATCCCGCTATGTGGCCTTAAGTCATCGTAAGGTTTGAAGTTTCTACTTTCGATCCTGCATGGAGAGCTATAATCTCAGCTCCCCCGCCCCCCCCACACACACCTCTGCACACACACCCCCCCCCAACACTGGGAGTAAACCAGGATGATGTCCGTCTTCTCATTCCCCATGTGACCGTTGGCAGTGTAGAGAGACTGATTGTCACAGCTAAAGGAAGAGGGACAACAGGGTCACTGGTGTCTACAGAGATTATATTCTACGTGTCTCACTGAATTTACACAACTCCAAGTGCCAACCACATCAAGGTCAGGAAATCCTGAACTGGAATAAGAAAGACCCAGAAGATGAATGTGAACAGATCCATTTGCTTCCCGACAGTGGGCACAGACTTCAGTCTCTGGCTACTGTTCCAAGACCCAGGGCTCTGCAATTGTGTGACATCCTTCAGTGAACCCACATGGGAAATTCTCCATGGAATTATCTTCAGCCCACTGTACTTCTGAATCCCTCTTCCTTCCTTCTGTGCCACACAGCAAGTCTGGCTTAAATGCTGCCTGATCTCCATTTCAAGTTTTCTGCCTCTGGATTTTTAGATCTCAAGACCATGGACGAAACATCAGTTACAGCAACAAAAGTGAATTTTCCGTGCAGAGACTTCTAGGGGTTCTGTTTGTTTTCAGGGTGCTAGAGATCACACTCAGATGCTCATATATGTTAGGTAAATGTTCTCCCACTGAGTTACAGCCCAGCTCACACAGAGACTTCTAAAAGAAAATACGGCCATGCTCTTTGAAATGGAGCATTGAGGGATGAAGTTTGGATGGCGAAGAAAACTTCTCACCAGCTCTCTCCCCACATTCGTGCCAAGCACTGCCTCCCTAGACTTCGGGTCACCATATCTGTACTACGTTTTGATACAGAAGGCTCGAGACCATTCAAGAGAATTATTTAGTACAC(SEQ ID NO: 59) >NP_848709.2 V-set domain containing T-cell activationinhibitor 1 precursor [Mus musculus]MASLGQIIFWSIINIIIILAGAIALIIGFGISGKHFITVTTFTSAGNIGEDGTLSCTFEPDIKLNGIVIQWLKEGIKGLVHEFKEGKDDLSQQHEMFRGRTAVFADQVVVGNASLRLKNVQLTDAGTYTCYIRTSKGKGNANLEYKTGAFSMPEINVDYNASSESLRCEAPRWFPQPTVAWASQVDQGANFSEVSNTSFELNSENVTMKVVSVLYNVTINNTYSCMIENDIAKATGDIKVTDSEVKRRSQLQLLNSGPSPCVFSSAFVAGWALLSLSCCLMLR (SEQ ID NO: 60)Human B7-H5 >NM_022153.2 Homo sapiens V-set immunoregulatory receptor(VISTA) (VSIR), mRNAAGTCGCGGGAGGCTTCCCCGCGCCGGCCGCGTCCCGCCCGCTCCCCGGCACCAGAAGTTCCTCTGCGCGTCCGACGGCGACATGGGCGTCCCCACGGCCCTGGAGGCCGGCAGCTGGCGCTGGGGATCCCTGCTCTTCGCTCTCTTCCTGGCTGCGTCCCTAGGTCCGGTGGCAGCCTTCAAGGTCGCCACGCCGTATTCCCTGTATGTCTGTCCCGAGGGGCAGAACGTCACCCTCACCTGCAGGCTCTTGGGCCCTGTGGACAAAGGGCACGATGTGACCTTCTACAAGACGTGGTACCGCAGCTCGAGGGGCGAGGTGCAGACCTGCTCAGAGCGCCGGCCCATCCGCAACCTCACGTTCCAGGACCTTCACCTGCACCATGGAGGCCACCAGGCTGCCAACACCAGCCACGACCTGGCTCAGCGCCACGGGCTGGAGTCGGCCTCCGACCACCATGGCAACTTCTCCATCACCATGCGCAACCTGACCCTGCTGGATAGCGGCCTCTACTGCTGCCTGGTGGTGGAGATCAGGCACCACCACTCGGAGCACAGGGTCCATGGTGCCATGGAGCTGCAGGTGCAGACAGGCAAAGATGCACCATCCAACTGTGTGGTGTACCCATCCTCCTCCCAGGATAGTGAAAACATCACGGCTGCAGCCCTGGCTACGGGTGCCTGCATCGTAGGAATCCTCTGCCTCCCCCTCATCCTGCTCCTGGTCTACAAGCAAAGGCAGGCAGCCTCCAACCGCCGTGCCCAGGAGCTGGTGCGGATGGACAGCAACATTCAAGGGATTGAAAACCCCGGCTTTGAAGCCTCACCACCTGCCCAGGGGATACCCGAGGCCAAAGTCAGGCACCCCCTGTCCTATGTGGCCCAGCGGCAGCCTTCTGAGTCTGGGCGGCATCTGCTTTCGGAGCCCAGCACCCCCCTGTCTCCTCCAGGCCCCGGAGACGTCTTCTTCCCATCCCTGGACCCTGTCCCTGACTCTCCAAACTTTGAGGTCATCTAGCCCAGCTGGGGGACAGTGGGCTGTTGTGGCTGGGTCTGGGGCAGGTGCATTTGAGCCAGGGCTGGCTCTGTGAGTGGCCTCCTTGGCCTCGGCCCTGGTTCCCTCCCTCCTGCTCTGGGCTCAGATACTGTGACATCCCAGAAGCCCAGCCCCTCAACCCCTCTGGATGCTACATGGGGATGCTGGACGGCTCAGCCCCTGTTCCAAGGATTTTGGGGTGCTGAGATTCTCCCCTAGAGACCTGAAATTCACCAGCTACAGATGCCAAATGACTTACATCTTAAGAAGTCTCAGAACGTCCAGCCCTTCAGCAGCTCTCGTTCTGAGACATGAGCCTTGGGATGTGGCAGCATCAGTGGGACAAGATGGACACTGGGCCACCCTCCCAGGCACCAGACACAGGGCACGGTGGAGAGACTTCTCCCCCGTGGCCGCCTTGGCTCCCCCGTTTTGCCCGAGGCTGCTCTTCTGTCAGACTTCCTCTTTGTACCACAGTGGCTCTGGGGCCAGGCCTGCCTGCCCACTGGCCATCGCCACCTTCCCCAGCTGCCTCCTACCAGCAGTTTCTCTGAAGATCTGTCAACAGGTTAAGTCAATCTGGGGCTTCCACTGCCTGCATTCCAGTCCCCAGAGCTTGGTGGTCCCGAAACGGGAAGTACATATTGGGGCATGGTGGCCTCCGTGAGCAAATGGTGTCTTGGGCAATCTGAGGCCAGGACAGATGTTGCCCCACCCACTGGAGATGGTGCTGAGGGAGGTGGGTGGGGCCTTCTGGGAAGGTGAGTGGAGAGGGGCACCTGCCCCCCGCCCTCCCCATCCCCTACTCCCACTGCTCAGCGCGGGCCATTGCAAGGGTGCCACACAATGTCTTGTCCACCCTGGGACACTTCTGAGTATGAAGCGGGATGCTATTAAAAACTACATGGGGAAACAGGTGCAAACCCTGGAGATGGATTGTAAGAGCCAGTTTAAATCTGCACTCTGCTGCTCCTCCCCCACCCCCACCTTCCACTCCATACAATCTGGGCCTGGTGGAGTCTTCGCTTCAGAGCCATTCGGCCAGGTGCGGGTGATGTTCCCATCTCCTGCTTGTGGGCATGCCCTGGCTTTGTTTTTATACACATAGGCAAGGTGAGTCCTCTGTGGAATTGTGATTGAAGGATTTTAAAGCAGGGGAGGAGAGTAGGGGGCATCTCTGTACACTCTGGGGGTAAAACAGGGAAGGCAGTGCCTGAGCATGGGGACAGGTGAGGTGGGGCTGGGCAGACCCCCTGTAGCGTTTAGCAGGATGGGGGCCCCAGGTACTGTGGAGAGCATAGTCCAGCCTGGGCATTTGTCTCCTAGCAGCCTACACTGGCTCTGCTGAGCTGGGCCTGGGTGCTGAAAGCCAGGATTTGGGGCTAGGCGGGAAGATGTTCGCCCAATTGCTTGGGGGGTTGGGGGGATGGAAAAGGGGAGCACCTCTAGGCTGCCTGGCAGCAGTGAGCCCTGGGCCTGTGGCTACAGCCAGGGAACCCCACCTGGACACATGGCCCTGCTTCTAAGCCCCCCAGTTAGGCCCAAAGGAATGGTCCACTGAGGGCCTCCTGCTCTGCCTGGGCTGGGCCAGGGGCTTTGAGGAGAGGGTAAACATAGGCCCGGAGATGGGGCTGACACCTCGAGTGGCCAGAATATGCCCAAACCCCGGCTTCTCCCTTGTCCCTAGGCAGAGGGGGGTCCCTTCTTTTGTTCCCTCTGGTCACCACAATGCTTGATGCCAGCTGCCATAGGAAGAGGGTGCTGGCTGGCCATGGTGGCACACACCTGTCCTCCCAGCACTTTGCAGGGCTGAGGTGGAAGGACCGCTTAAGCCCAGGTGTTCAAGGCTGCTGTGAGCTGTGTTCGAGCCACTACACTCCAGCCTGGGGACGGAGCAAAACTTTGCCTCAAAACAAATTTTAAAAAGAAAGAAAGAAGGAAAGAGGGTATGTTTTTCACAATTCATGGGGGCCTGCATGGCAGGAGTGGGGACAGGACACCTGCTGTTCCTGGAGTCGAAGGACAAGCCCACAGCCCAGATTCCGGTTCTCCCAACTCAGGAAGAGCATGCCCTGCCCTCTGGGGAGGCTGGCCTGGCCCCAGCCCTCAGCTGCTGACCTTGAGGCAGAGACAACTTCTAAGAATTTGGCTGCCAGACCCCAGGCCTGGCTGCTGCTGTGTGGAGAGGGAGGCGGCCCGCAGCAGAACAGCCACCGCACTTCCTCCTCAGCTTCCTCTGGTGCGGCCCTGCCCTCTCTTCTCTGGACCCTTTTACAACTGAACGCATCTGGGCTTCGTGGTTTCCTGTTTTCAGCGAAATTTACTCTGAGCTCCCAGTTCCATCTTCATCCATGGCCACAGGCCCTGCCTACAACGCACTAGGGACGTCCCTCCCTGCTGCTGCTGGGGAGGGGCAGGCTGCTGGAGCCGCCCTCTGAGTTGCCCGGGATGGTAGTGCCTCTGATGCCAGCCCTGGTGGCTGTGGGCTGGGGTGCATGGGAGAGCTGGGTGCGAGAACATGGCGCCTCCAGGGGGCGGGAGGAGCACTAGGGGCTGGGGCAGGAGGCTCCTGGAGCGCTGGATTCGTGGCACAGTCTGAGGCCCTGAGAGGGAAATCCATGCTTTTAAGAACTAATTCATTGTTAGGAGATCAATCAGGAATTAGGGGCCATCTTACCTATCTCCTGACATTCACAGTTTAATAGAGACTTCCTGCCTTTATTCCCTCCCAGGGAGAGGCTGAAGGAATGGAATTGAAAGCACCATTTGGAGGGTTTTGCTGACACAGCGGGGACTGCTCAGCACTCCCTAAAAACACACCATGGAGGCCACTGGTGACTGCTGGTGGGCAGGCTGGCCCTGCCTGGGGGAGTCCGTGGCGATGGGCGCTGGGGTGGAGGTGCAGGAGCCCCAGGACCTGCTTTTCAAAAGACTTCTGCCTGACCAGAGCTCCCACTACATGCAGTGGCCCAGGGCAGAGGGGCTGATACATGGCCTTTTTCAGGGGGTGCTCCTCGCGGGGTGGACTTGGGAGTGTGCAGTGGGACAGGGGGCTGCAGGGGTCCTGCCACCACCGAGCACCAACTTGGCCCCTGGGGTCCTGCCTCATGAATGAGGCCTTCCCCAGGGCTGGCCTGACTGTGCTGGGGGCTGGGTTAACGTTTTCTCAGGGAACCACAATGCACGAAAGAGGAACTGGGGTTGCTAACCAGGATGCTGGGAACAAAGGCCTCTTGAAGCCCAGCCACAGCCCAGCTGAGCATGAGGCCCAGCCCATAGACGGCACAGGCCACCTGGCCCATTCCCTGGGCATTCCCTGCTTTGCATTGCTGCTTCTCTTCACCCCATGGAGGCTATGTCACCCTAACTATCCTGGAATGTGTTGAGAGGGATTCTGAATGATCAATATAGCTTGGTGAGACAGTGCCGAGATAGATAGCCATGTCTGCCTTGGGCACGGGAGAGGGAAGTGGCAGCATGCATGCTGTTTCTTGGCCTTTTCTGTTAGAATACTTGGTGCTTTCCAACACACTTTCACATGTGTTGTAACTTGTTTGATCCACCCCCTTCCCTGAAAATCCTGGGAGGTTTTATTGCTGCCATTTAACACAGAGGGCAATAGAGGTTCTGAAAGGTCTGTGTCTTGTCAAAACAAGTAAACGGTGGAACTACGACTAAA (SEQ ID NO: 61) >NP_071436.1 V-type immunoglobulin domain-containingsuppressor of T-cell activation precursor [Homo sapiens]MGVPTALEAGSWRWGSLLFALFLAASLGPVAAFKVATPYSLYVCPEGQNVTLTCRLLGPVDKGHDVTFYKTWYRSSRGEVQTCSERRPIRNLTFQDLHLHHGGHQAANTSHDLAQRHGLESASDHHGNFSITMRNLTLLDSGLYCCLVVEIRHHHSEHRVHGAMELQVQTGKDAPSNCVVYPSSSQDSENITAAALATGACIVGILCLPLILLLVYKQRQAASNRRAQELVRMDSNIQGIENPGFEASPPAQGIPEAKVRHPLSYVAQRQPSESGRHLLSEPSTPLSPPGPGDVFFPSLDPVPDSPNFEVI (SEQ ID NO: 62) Mouse B7-H5>NM_028732.4 Mus musculus V-set immunoregulatory receptor (VISTA)(Vsir), transcript variant 1, mRNAGGGGGCGCTGCTGGGCGGGGAGCTTGCTCGGCCGCCTGCCTCGCCTTGGGCTCAGCATTCACTCTAGCGAGCGAGCGGCGTGTACAGCCGGCTCCCTGGGCTCCTGGAGTCCCGCTTGCTCCAAGCGCACTCCAGCAGTCTCTTTCTGCTCTTGCCCGGCTCGACGGCGACATGGGTGTCCCCGCGGTCCCAGAGGCCAGCAGCCCGCGCTGGGGAACCCTGCTCCTTGCTATTTTCCTGGCTGCATCCAGAGGTCTGGTAGCAGCCTTCAAGGTCACCACTCCATATTCTCTCTATGTGTGTCCCGAGGGACAGAATGCCACCCTCACCTGCAGGATTCTGGGCCCCGTGTCCAAAGGGCACGATGTGACCATCTACAAGACGTGGTACCTCAGCTCACGAGGCGAGGTCCAGATGTGCAAAGAACACCGGCCCATACGCAACTTCACATTGCAGCACCTTCAGCACCACGGAAGCCACCTGAAAGCCAACGCCAGCCATGACCAGCCCCAGAAGCATGGGCTAGAGCTAGCTTCTGACCACCACGGTAACTTCTCTATCACCCTGCGCAATGTGACCCCAAGGGACAGCGGCCTCTACTGCTGTCTAGTGATAGAATTAAAAAACCACCACCCAGAACAACGGTTCTACGGGTCCATGGAGCTACAGGTACAGGCAGGCAAAGGCTCGGGGTCCACATGCATGGCGTCTAATGAGCAGGACAGTGACAGCATCACGGCTGCGGCCCTGGCCACCGGCGCCTGCATCGTGGGAATCCTCTGCCTCCCCCTTATCCTGCTGCTGGTCTATAAGCAGAGACAGGTGGCCTCTCACCGCCGTGCCCAGGAGTTGGTGAGGATGGACAGCAGCAACACCCAAGGAATCGAAAACCCAGGCTTCGAGACCACTCCACCCTTCCAGGGGATGCCTGAGGCCAAGACCAGGCCGCCACTGTCCTATGTGGCCCAGCGGCAACCTTCGGAGTCAGGACGGTACCTGCTCTCTGACCCCAGCACACCTCTGTCGCCTCCAGGCCCTGGGGACGTCTTTTTCCCATCCCTAGATCCAGTCCCTGACTCCCCTAACTCTGAAGCCATCTAAACCAGCTGGGGAACCATGAACCATGGTACCTGGGTCAGGGATATGTGCACTTGATCTATGGCTGGCCCTTGGACAGTCTTTTAGGCACTGACTCCAGCTTCCTTGCTCCTGCTCTGAGCCTAGACTCTGCTTTTACAAGATGCACAGACCCTCCCCTATCTCTTTCAGACGCTACTTGGGGGGCAGGGAGAAGATGTTGGATTGCTCATTGCTGTTCTCAAGATCTTGGGATGCTGAGTTCTCCCTAGAGACTTGACTTCGACAGCCACAGATGTCAGATGACCTGCATCCTATGAACGTCCGGCTTGGCAAGAGCCTTTCTTCATGGAAACCAGTAGCCCGGAGGGGATGAGGTAGGCACCTTGCCACCCTCCCGGGAGAGAGACACAAGATGTGAGAGACTCCTGCTCACTGTGGGGGTGTGGCTGGCCTGCTTGTTTGCCTGAGGATGCTCCTCTGTTGGACTGACTCTATCCCCCTGGATTCTGGAGCTTGGCTGGCCTATGTCCCACCAGAGGAGCATCTCAGCAGCCTTCCACCAGCAACCTGAGGGCCTGCCAGCTTCGTGGCTCTGGGCTCTCATTACCTGTATGGCCGTCCACAGAGCTCAGTGGCCAGAGGCTTTGAAACAGGAAGTACATGTCAGGTTCAGGAACCACTGTGAGCTCATTAGTGTCTTGAGCAATGTGAGGCCTGGACCAGTGGACACGGAGGGAGGGTGGCGAGAGGATGATGGGGATGATGAGGGGAACACGCTCCCTTCCTGTCCTTGTCATCCACCACTACCACTATTCAGTGTGGAGCAGTGGCAAAGGTGACCGACCTCCACAATGTCCTAGTGATGCTGGACCATTTCTAAGTGTGAAAGAGATGCTATTAAAAACAGTATGTGGCAATGGCTGCCAACAGCTGAGTGGACTGGAGGCACTGGCTTTAAGGCCCTGGAGGTGCAGGGCCCGGTATGGGGATAGGGATGGGAGTTTCAGTGAGGGCCTAGGGATCACTCCGCTTCTGACCACTCTTCTTCTGAGCCTCACCTCAGGGTGACCTTCAGGCACACAGAAGAGCTTGCCCCTGGTCCGATACTACTCTTGGCTCTCATCTCCAGGGTTTGGCATGACCTGGGCACACAGGGGGAGTCTTCAGAAAGGATTTTAAAGCATGAAAAGAAAGGGTAGTTCTTGTGAGGTAGGGATGGGCAGCTGATGTTTGAGAGTGAGGAGGGATACGGCTGGGCAGATCACTCTCCAGTCTCTAGAGGGAAAGTAGCTCTAAGTCTGGGAGAGCAGCAGCCCAGTGGTACCATATGTCTTCTTGCAGCTTCCACTGGCTGGGCTGAACTGGGCATGGGTAGGAAAGCTCCTGTTOTGGGCCTGCAGCCAGGGAGAACCCCATTCATTCCCTGAGGACAGATGGGTGGGGAGAGAAGAGAGAGTTTCAGGCCGGGAAGCAGCAATAAGCTATCTGCTGGGGACCCAGACAAGTTGTCTGATGAGGTCCAAGATGTGGGATGCCAGTTATACCTGGGGCTTGGGGATCCTTAGAGGCTTTGTATCATCATCATAGGAGTGTCGGGGTGGCCAGGGCATCAAAGCCATGACCCCTGTTTTATCCTCAGGGTCCACTCTTCTGCACCATCCATTGCTCTAGATCTATGCAGTTACTATAGACAGAATGTGTTGTTCTGTTTGGCTTTGGGGATAATGGCCTGGCGAACTGCCAGCTGTTCAGTGGCAGGGCTGTGAGGCCAGTCAAAGACTAGAACCCACAGACCAGCTGAACGATGAGTATAGCCTGTCCCCTGGGGGAGCCTGACCTGTCTCCAGCCCTAAGCTTCAGACCTCACCACTCAGATGACTTCTAAGAATTTGCCTGTGGGGACCCCTGCATGGCTGCAGCTCCGTGGAAAGGAGAGGAGGCCCCCAGCAGAAGAACCACTCGCTTCCTGCCCAGCTTCCTCCTGTAGGGCTCTAAGTCTCTTCTTCTTGGGACCCTGCAAGCAAAGGCATGTCAGCTTGGTGGTTTCCTGTTTTGGGTGAAGTTTTGTGTGGTCCGGGTTCTGTCTACATCCATGAACTTGGGTGCTACCACCTTGCTGCTGCTGTAGAGACAGCTGCAGGATCTTAGGGTGGAAAATGGAGGTGCCCTGAGGTGCTAGCCCTTGGGGCAAAAGATGGGGTGGCAATGAGACACAGTGGGGAACTGAGTTCCCCAAGAGGAGGGAGGAGCCCTGTAGCCTCAAGGGCCATATTGGGTTCCTGGTACCAGCAAAAGCCTAGAGAGCGAAGTCTGTATTTTGAGGAGGTAATTGATCCTTACGGAATCCATCAGAAATTTGGAGCGGGTGCTTTATCTATCTCTGGAGGGTCTCTACCTATCTCCGATGAAGCTCTCCCTGGGCCTGGGATGGGAGAAACCAGGAGGAAAGGTGTCTGATAAAGCAGGGGCTTCTTGACAAGCCAAAGGGCCACTGGTAGCTGTTGTGGACCGAGCTGACCCTGCTGAAGTATTGTAGTGTGCCTTGGACCAACTTCTCAAAAGAGCAACCCCGGGGCTACCCTACTTCTGCCAGGAAGAGGCGGAGAAGGGGCTGAGAGGCCTGGAAGGGGCTAGCTCCTTCTTTGAGAACTGCTCCCCGGAGGACTTGGAGGAGGCGGCTAGGCTACGGGCTGCTGAGGGCCCTTTGTCTTTCCTAACCTGGGCACTGTTAGGATGCTCCCTCCTGGAAAAGGCTTTCCTGGGTGTGAGCTAGAGCAGTGTCCATGCCAGCGCTGAACCTGCCATGGTGGGAGCTGAACTAAAAATTTCTCAGGGAACTAAAATAGGCAAAAGAGGAACTGGGGGAGGAGGGTGCCAGGCAGGATGGGGGGAAGGGAGGGCAGTGCAAAAGTCTCTTGAAACACAGACAGCCCAGCTGAGTGCCAGTCCCAGATCACAGAGAATACGGCTCATCTGGCTCATGTTCTGCATGCTTGCTGCTTTACCCTGGCACTTTCCTTCTCCACCATGAGTGCGAGTCCTGGGAGTCCTGGGAGGGTGAGGATTAATGCCAGCCTGGGGAGCAGATAGCTGACAGAGTCCTTGGGTAACTGGCTTGAACCAGGACCTCAGGATTCCACTCTGGGGATCTAGCTTTGTCTGGGCCAGTGAAGATCTCTATAATGGCATTATTGCCAGGGGATAAACATTTCACTGGGTTCTGATCTGTTGGGTGTGGCTTCCTGGAAAATATGGTGAGAGGAATTCTGCTAAGGATACAGTTGATAAGAAAGTTCTGAGATTGATTAGTAATGCCTGCCTTGGACTCAGGAAGGGAAGTGGCAGTATGAATGCCATGTCTTAATCATTTTGGTTAAAATATGCTTCCCAAAAGATTTCCACGTGTGTTCTTGTTTATTTGACATCTGTCTCCATATCAGTCTTGAAAGCCTTTCTGTGTGTATATATATGATGTTTGCGTGTATATATGTTTTTGTGTGTGCATATGGAAGTCAGAAATCACTGGGTGTCTTCCTCCATTCCTTTGCAATGTATGTTTTTTTTTTTTTTACGATTTATTTACTATATGAATGTTTTGCCTGAATACATGCATAGGTGTCACGTACATGCCTGCTGGAACGCTTGGAACTGGAGTTACAGGTGGCTATGAGCTACAGTGTGAGCACTGGGAATCAAACCTGGGTCTTCTGCAAGAGCAACAAATTAAAAGTCAGCTCTTAACTACTTGAGCTATTTTTCCAACTCC (SEQ ID NO: 63) >NP_083008.1 V-type immunoglobulin domain-containingsuppressor of T-cell activation isoform 1 precursor [Mus musculus]MGVPAVPEASSPRWGTLLLAIFLAASRGLVAAFKVTTPYSLYVCPEGQNATLTCRILGPVSKGHDVTIYKTWYLSSRGEVQMCKEHRPIRNFTLQHLQHHGSHLKANASHDQPQKHGLELASDHHGNFSITLRNVTPRDSGLYCCLVIELKNHHPEQRFYGSMELQVQAGKGSGSTCMASNEQDSDSITAAALATGACIVGILCLPLILLLVYKQRQVASHRRAQELVRMDSSNTQGIENPGFETTPPFQGMPEAKTRPPLSYVAQRQPSESGRYLLSDPSTPLSPPGPGDVFFPSLDPVPDSPNSEAI (SEQ ID NO: 64) Human B7-H7>NM_007072.4 Homo sapiens HERV-H LTR-associating 2 (HHLA2)(HHLA2), transcript variant 1, mRNAAGTTCTCTTCAAGTCATGTAATCGACTTTTTTGAATTAGTTTTCAGTTTCATTTTGTTTTCCCTAATTCAAGTTGGGAACACTTCATTTTCCCCAATTCAAGTTGGGAACACTTCCTTGGTATTTCCTTGCTACATGGACTTTAGCAAATGCTACTTTACTCTCCTTCCAGCTACTCAGGAGGCTGAGGCAGGAGAATCGCTTGAACCCGGGAGGCGGAGGTTACAGTGAGCCTTTTCCTAGTTTTACTGTTGGAAGCCTAACTCACAGGAGAGATTATGCAATACAGTCCTGAAGTCAAGGGAGGAGAGCATGTAGGAGAATACTAACCCTGCACAGATTGTGATGGTGATGTGGAATATACTAAAGCCTAGAACGCACCTCCTCTGCATGACTAATATGTTCTGCACAAGACATGAAGGCACAGACAGCACTGTCTTTCTTCCTCATTCTCATAACATCTCTGAGTGGATCTCAAGGCATATTCCCTTTGGCTTTCTTCATTTATGTTCCTATGAATGAACAAATCGTCATTGGAAGACTTGATGAAGATATAATTCTCCCTTCTTCATTTGAGAGGGGATCCGAAGTCGTAATACACTGGAAGTATCAAGATAGCTATAAGGTTCACAGTTACTACAAAGGCAGTGACCATTTGGAAAGCCAAGATCCCAGATATGCAAACAGGACATCCCTTTTCTATAATGAGATTCAAAATGGGAATGCGTCGCTATTTTTCAGAAGAGTAAGCCTTCTGGACGAAGGAATTTACACCTGCTATGTAGGAACAGCAATTCAAGTGATTACAAACAAAGTGGTGCTAAAGGTGGGAGTTTTTCTCACACCCGTGATGAAGTATGAAAAGAGGAACACAAACAGCTTCTTAATATGCAGCGTGTTAAGTGTTTATCCTCGTCCAATTATCACGTGGAAAATGGACAACACACCTATCTCTGAAAACAACATGGAAGAAACAGGGTCTTTGGATTCTTTTTCTATTAACAGCCCACTGAATATTACAGGATCAAATTCATCTTATGAATGTACAATTGAAAATTCACTGCTGAAGCAAACATGGACAGGGCGCTGGACGATGAAAGATGGCCTTCATAAAATGCAAAGTGAACACGTTTCACTCTCATGTCAACCTGTAAATGATTATTTTTCACCAAACCAAGACTTCAAAGTTACTTGGTCCAGAATGAAAAGTGGGACTTTCTCTGTCCTGGCTTACTATCTGAGCTCCTCACAAAATACAATTATCAATGAATCCCGATTCTCATGGAACAAAGAGCTGATAAACCAGAGTGACTTCTCTATGAATTTGATGGATCTTAATCTTTCAGACAGTGGGGAATATTTATGCAATATTTCTTCGGATGAATATACTTTACTTACCATCCACACAGTGCATGTAGAACCGAGCCAAGAAACAGCTTCCCATAACAAAGGCTTATGGATTTTGGTGCCCTCTGCGATTTTGGCAGCTTTTCTGCTGATTTGGAGCGTAAAATGTTGCAGAGCCCAGCTAGAAGCCAGGAGGAGCAGACACCCTGCTGATGGAGCCCAACAAGAAAGATGTTGTGTCCCTCCTGGTGAGCGCTGTCCCAGTGCACCCGATAATGGCGAAGAAAATGTGCCTCTTTCAGGAAAAGTATAGGAAATGAGAGAAGACTGTGACAACTCATGACCTGCATCCTTAATATCCAGTGACTTCATCTCCCCTTTCTTCACCACAATTCCAGGCAATGGCCTGTCGGAGCAGACAATTCTACCACTGCAAAGAGTTGTAACCATTTTCTGGTATCACATTTATTTTTCAAGACATACTTTTCAAGACATCATTCACTGACCCACTACCTGCATTGAGTATAAATGCCTGGATGTTAAGGATTCCAATTTAACTTTGAAAAGAACTGTCTCATTCATTTACATTTCTGTTACAGTCAGCCCAGGAGGTTACAGTGAGCTCTCCACTAAGAATCTGGAAGAAATGCATCACTAGGGGTTGATTCCCAATCTGATCAACTGATAATGGGTGAGAGAGCAGGTAAGAGCCAAAGTCACCTTAGTGGAAAGGTTAAAAACCAGAGCCTGGAAACCAAGATGATTGATTTGACAAGGTATTTTAGTCTAGTTTTATATGAACGGTTGTATCAGGGTAACCAACTCGATTTGGGATGAATCTTAGGGCACCAAAGACTAAGACAGTATCTTTAAGATTGCTAGGGAAAAGGGCCCTATGTGTCAGGCCTCTGAGCCCAAGCCAAGCATCGCATCCCCTGTGATTTGCACGTATACATCCAGATGGCCTAAAGTAACTGAAGATCCACAAAAGAAGTAAAAATAGCCTTAACTGATGACATTCCACCATTGTGATTTGTTCCTGCCCCACCCTAACTGATCAATGTACTTTGTAATCTCCCCCACCCTTAAGAAGGTACTTTGTAATCTTCCCCACCCTTAAGAAGGTTCTTTGTAATTCTCCCCACCCTTGAGAATGTACTTTGTGAGATCCACCCTGCCCACAAAACATTGCTCTTAACTTCACCGCCTAACCCAAAACCTATAAGAACTAATGATAATCCATCACCCTTCGCTGACTCTCTTTTCGGACTCAGCCCACCTGCACCCAGGTGAAATAAACAGCTTTATTGCTCACACAAA (SEQ ID NO:65) >NP_009003.1 HERV-H LTR-associating protein 2 isoform aprecursor [Homo sapiens]MKAQTALSFFLILITSLSGSQGIFPLAFFIYVPMNEQIVIGRLDEDIILPSSFERGSEVVIHWKYQDSYKVHSYYKGSDHLESQDPRYANRTSLFYNEIQNGNASLFFRRVSLLDEGIYTCYVGTAIQVITNKVVLKVGVFLTPVMKYEKRNTNSFLICSVLSVYPRPIITWKMDNTPISENNMEETGSLDSFSINSPLNITGSNSSYECTIENSLLKQTWTGRWTMKDGLHKMQSEHVSLSCQPVNDYFSPNQDFKVTWSRMKSGTFSVLAYYLSSSQNTIINESRFSWNKELINQSDFSMNLMDLNLSDSGEYLCNISSDEYTLLTIHTVHVEPSQETASHNKGLWILVPSAILAAFLLIWSVKCCRAQLEARRSRHPADGAQQERCCVPPGERCPSAPDNGEENVPLSGKV (SEQ ID NO: 66 Mouse BTNL1>NM_001111094.1 Mus musculus butyrophilin-like 1 (Btnl1), mRNAACCCTTAAATAAGAGCTGAAGATGGCTGCAGCTTTCTCCTAGACTCCTCCAGGAGAAACTCTAAAGCCAGAGCCTGGGGGCAGCATTGTGTGTCCACCTTGCCACTGAGAACATCTACGGAAATTGGACACTCTGGCCCCAGCATCCACACGCTTGACTGTTGGCCACAGTAACACAGGTGTGGATGGTCCCCAGAGCCAGGGTCCAGGAGTGCACTGAGGATCCCTGGGGCTTCAAGGAACCCACAGCTCTGTCCAGACGGGAATTTTTTTCCTGAGAACTTTCACCTGTTGCCCTCCTATGGTGAACCTGGACTTGACCTTCCACTCTGATGATGAAGGGCTCCCCCTCCGTCCCTCCAGCTGGTTGTCTCCTCCCTCTGCTCCTCCTGCTGTTTACCGGAGTCTCTGGAGAAGTGTCTTGGTTTTCTGTGAAGGGACCAGCTGAGCCCATCACTGTCCTGCTGGGGACTGAAGCCACCCTGCCCTGCCAGCTGTCTCCTGAACAGAGTGCAGCTCGCATGCACATCCGATGGTACCGTGCCCAGCCCACCCCTGCTGTGCTGGTGTTCCACAACGGACAGGAGCAGGGAGAGGTGCAGATGCCGGAATACAGGGGCAGGACCCAGATGGTGAGACAAGCCATTGACATGGGAAGTGTGGCTCTGCAGATACAGCAGGTCCAGGCCTCTGATGATGGCCTGTACCACTGTCAGTTTACAGATGGCTTCACCTCCCAAGAGGTCTCCATGGAGCTTCGAGTCATAGGTTTAGGCTCTGCCCCTCTTGTTCACATGACAGGACCTGAGAATGATGGGATCCGAGTGTTGTGCTCCTCAAGTGGCTGGTTCCCAAAACCCAAAGTGCAATGGAGAGACACCTCCGGGAACATGCTACTGTCCTCCTCTGAGTTGCAGACCCAAGACAGAGAAGGGCTCTTCCAGGTGGAAGTGTCTCTTTTGGTCACAGATAGAGCTATTGGCAATGTGATCTGCTCCATCCAAAATCCCATGTATGACCAGGAGAAATCGAAGGCCATCCTCCTCCCAGAGCCCTTCTTCCCCAAGACGTGTCCATGGAAAGTAGCCCTGGTTTGTTCTGTCCTCATACTATTGGTCCTGCTCGGTGGGATCAGCCTTGGAATCTGGAAAGAACATCAAGTCAAAAGGAGAGAAATTAAAAAATGGTCAAAGGAACATGAAGAAATGCTTCTGTTGAAGAAGGGGACAAAATCTGTACTGAAGATCAGAGATGACCTCCAGGCCGACCTAGATCGGAGGAAGGCGCTGTACAAAGAAGACTGGAAGAAGGCCTTGCTGTACCCTGACTGGAGGAAGGAGCTGTTCCAGGAGGCTCCTGTGAGGATAAATTATGAAATGCCTGACCAGGACAAGACAGACTCAAGGACAGAAGAGAACAGAGGTGAGGAGACTGTCAGCAGCTCACAAGTAGACCACAACCTCATCACACTCTCCCAGGAAGGCTTCATGTTGGGAAGATACTACTGGGAGGTGGATGTCAAGGACACAGAGGAGTGGACACTAGGAGTTTATGAGCTGTGCACTCAGGATGCATCACTTACAGACCCCTTGAGGAAATTCAGAGTCCTGGAAAAGAATGGAGATGGATACAGGGCTCTTGACTTCTGTTCCCAAAACATTAATTCGGAAGAACCTCTGCAACTGAAGACACGTCCGCTGAAGATCGCCATCTTCTTGGATCAGGAAGACAATGACCTCTCTTTCTACAACATGACCGATGAGACACACATCTTTTCCTTTGCCCAGGTCCCTTTCTTGGGATCACCCTATCCTTACTTCACACGTAATTCCATGGGGCTCTCTGCAACAGCACAGCCCTAAGTGATGTGCACAGGGAATTCAATGGGTGGGTGCTGCAGCGTGCTACCCGTAAGGCCCTCTTAGGCAGGCACAGGGGGCCTCTGACCAAGAGGCCTCTTAACCTGAGACTCCATGAGCCTCGGGGATCAGATCCTGGACAAGATTCTCGGACCATCTGTGTCGTGCATGGTGTTATAGTTATTAATAGCCTTCCTTCTTTTGACAAAAATGTGTTTAATCATTCCTAAGATAAATGAATCCATGGCTTTCTGA (SEQ ID NO: 67) >NP_001104564.1 butyrophilin-like protein 1 precursor[Mus musculus] MMKGSPSVPPAGCLLPLLLLLFTGVSGEVSWFSVKGPAEPITVLLGTEATLPCQLSPEQSAARMHIRWYRAQPTPAVLVFHNGQEQGEVQMPEYRGRTQMVRQAIDMGSVALQIQQVQASDDGLYHCQFTDGFTSQEVSMELRVIGLGSAPLVHMTGPENDGIRVLCSSSGWFPKPKVQWRDTSGNMLLSSSELQTQDREGLFQVEVSLLVTDRAIGNVICSIQNPMYDQEKSKAILLPEPFFPKTCPWKVALVCSVLILLVLLGGISLGIWKEHQVKRREIKKWSKEHEEMLLLKKGTKSVLKIRDDLQADLDRRKALYKEDWKKALLYPDWRKELFQEAPVRINYEMPDQDKTDSRTEENRGEETVSSSQVDHNLITLSQEGFMLGRYYWEVDVKDTEEWTLGVYELCTQDASLTDPLRKFRVLEKNGDGYRALDFCSQNINSEEPLQLKTRPLKIAIFLDQEDNDLSFYNMTDETHIFSFAQVPFLGSPYPYFTRNSMGLSATAQP (SEQ ID NO: 68)Human VSIG8 >NM_001013661.1 Homo sapiens V-set and immunoglobulindomain containing 8 (VSIG8), mRNAACTCATTGCACCTTCCTGCCACCCCAGGCAGTGTCTGGGCCCTCAGCTCCCCCTCCCTCCACCTACCCCCTCACACCCACCACTACGACCCCACGGGATACCCAGCCCAGACGGAGGAAACACCGAGCCTAGAGACATGAGAGTTGGAGGAGCATTCCACCTTCTACTCGTGTGCCTGAGCCCAGCACTGCTGTCTGCTGTGCGGATCAACGGGGATGGACAGGAGGTCCTGTACCTGGCAGAAGGTGATAATGTGAGGCTGGGCTGCCCCTACGTCCTGGACCCTGAGGACTATGGTCCCAATGGGCTGGACATCGAGTGGATGCAGGTCAACTCAGACCCCGCCCACCACCGAGAGAACGTGTTCCTTAGTTACCAGGACAAGAGGATCAACCATGGCAGCCTTCCCCATCTGCAGCAGAGGGTCCGCTTTGCAGCCTCAGACCCAAGCCAGTACGATGCCTCCATCAACCTCATGAACCTGCAGGTATCTGATACAGCCACTTATGAGTGCCGGGTGAAGAAGACCACCATGGCCACCCGGAAGGTCATTGTCACTGTCCAAGCACGACCTGCAGTGCCCATGTGCTGGACAGAGGGCCACATGACATATGGCAACGATGTGGTGCTGAAGTGCTATGCCAGTGGGGGCTCCCAGCCCCTCTCCTACAAGTGGGCCAAGATCAGTGGGCACCATTACCCCTATCGAGCTGGGTCTTACACCTCCCAGCACAGCTACCACTCAGAGCTGTCCTACCAGGAGTCCTTCCACAGCTCCATAAACCAAGGCCTGAACAATGGGGACCTGGTGTTGAAGGATATCTCCAGAGCAGATGATGGGCTGTATCAGTGCACAGTGGCCAACAACGTGGGCTACAGTGTTTGTGTGGTGGAGGTGAAGGTCTCAGACTCCCGGCGTATAGGCGTGATCATCGGCATCGTCCTGGGCTCTCTGCTCGCGCTGGGCTGCCTGGCCGTAGGCATCTGGGGGCTCGTCTGCTGCTGCTGCGGGGGCTCCGGGGCTGGCGGCGCCCGCGGTGCCTTCGGCTACGGCAACGGCGGCGGGGTCGGCGGAGGGGCCTGCGGCGACTTGGCTAGTGAGATCAGAGAGGACGCCGTGGCGCCCGGGTGCAAGGCCAGCGGGCGCGGCAGCCGCGTCACCCACCTCCTGGGGTACCCGACGCAGAACGTCAGCCGCTCCCTGCGCCGCAAGTACGCGCCTCCCCCCTGCGGCGGCCCCGAGGACGTGGCCCTGGCGCCCTGCACCGCCGCCGCCGCCTGCGAAGCGGGCCCCTCCCCGGTCTACGTCAAGGTCAAGAGCGCGGAGCCGGCTGACTGCGCCGAGGGGCCGGTGCAGTGCAAGAACGGCCTCTTGGTGTGAGCGCGCGCGCCGGGCCGGGCTGCGCCCCAGCCAGGAGGAGGGCGCGGGGCTCTCTGTCTGCAGCTGGGGACACGTCGGGGCTGGGGACGACCTCGCTCGCCCCAGGCTGCCAGGCGGCTGGGGGTGAAGGCATTTCCCTAAGGAAATGCGTAGGGAGGCAGAGCCTCCTCCCCAAAAGTGGGAAGGGGCGGGCGAGGGCGGAGGAAGGCGATCCTGAGCCTTCTCCGCACCCCCGGGACCGAAGGCTTGGGGGAGAGGGAGGGAGGAGGAGGCTGAGTGTCCTAGAGCGGCTGAGGCCGGAGGCCTGGTGTCCCCAGCCTAAGCAGAGGGCCCCGGGGGCCGGGTGGGTGGGGGTCTGTCTGGACGAATTGTTCTGTGTGTGAGGTCTGAGCTCTGAGGCAGCAGTGTTAGCACAATAAAGAAACATTGAGACGTGA (SEQID NO: 69) >NP_001013683.1 V-set and immunoglobulin domain-containing protein 8 precursor [Homo sapiens]MRVGGAFHLLLVCLSPALLSAVRINGDGQEVLYLAEGDNVRLGCPYVLDPEDYGPNGLDIEWMQVNSDPAHHRENVFLSYQDKRINHGSLPHLQQRVRFAASDPSQYDASINLMNLQVSDTATYECRVKKTTMATRKVIVTVQARPAVPMCWTEGHMTYGNDVVLKCYASGGSQPLSYKWAKISGHHYPYRAGSYTSQHSYHSELSYQESFHSSINQGLNNGDLVLKDISRADDGLYQCTVANNVGYSVCVVEVKVSDSRRIGVIIGIVLGSLLALGCLAVGIWGLVCCCCGGSGAGGARGAFGYGNGGGVGGGACGDLASEIREDAVAPGCKASGRGSRVTHLLGYPTQNVSRSLRRKYAPPPCGGPEDVALAPCTAAAACEAGPSPVYVKVKSAEPADCAEGPVQCKNGLLV (SEQ ID NO: 70) Mouse VSIG8>NM_177723.4 Mus musculus V-set and immunoglobulin domaincontaining 8 (Vsig8), transcript variant 1, mRNAACTCATTGCATCTTCCTGCCACCCCGGGCAGTGTCTGGGCCCTCCGCTCCCCCTCCCTCCACCTGCCCCTTCCACCCACCACCACCAGCCCACTGGAGCCCAGCTCAGGCGGAGGAAAGACCAAGCCTAGAGACATGGGAGTTCGAGGAGCACTCCATCTTCTACTTGTGTGCCTGAGCCCAGCACTGTTGTCTGCTGTAAGGATCAACGGGGATGGCCAGGAGGTCATGTACCTGGCAGAAGGTGACAATGTGAGGCTAGGCTGTCCCTACCTCCTGGATCCTGAGGATTTGGGTACCAACAGTCTGGACATTGAGTGGATGCAAGTCAACTCAGAGCCCTCACACAGGGAGAATGTTTTTCTTACTTATCAAGACAAGAGGATAGGTCATGGCAACCTCCCCCATCTGCAGCAGAGGGTCCGCTTTGCAGCCTCAGACCCCAGCCAGTACGATGCCTCCATCAACCTCATGAACCTGCAGGTATCTGACACAGCAACCTATGAGTGCCGGGTGAAGAAGACCACCATGGCCACCAGGAAGGTCATTGTCACTGTCCAAGCACGTCCTGCGGTGCCCATGTGTTGGACGGAAGGCCACATGTCAAAGGGCAACGATGTGGTGCTGAAGTGCTTTGCCAACGGAGGCTCTCAGCCCCTCTCCTACAAGTGGGCCAAGATCAGTGGGCACAGTCACCCCTACCGAGCTGGGGCTTACCACTCACAGCACAGCTTCCACTCTGAGCTTTCTTACCAAGAGTCATTCCACAGCACCATCAACCAAGGCCTGGGCAACGGAGACCTGCTGTTGAAGGGCATCAACGCAGACGACGATGGGCTGTATCAGTGCACAGTGGCCAACCATGTGGGCTACAGCGTCTGTGTGGTAGAGGTGAAAGTCTCAGACTCCCAGCGAGTAGGCATGATCGTTGGAGCAGTGCTGGGCTCTTTGCTCATGCTGGCCTGCCTGGCACTAGGCATCTGGGGGCTCATCTGCTGCTGCTGCGGAGGCGGCGGGGCCGGTGGTGCCCGAGGTGCCTTCGGCTACGGGGTCGGCGGCGGGGTCGGCGGAGGGGCCTGCGGCGACTTGGCTAGTGAGATCAGAGTGGACGCCGAGGCGCCCGGGTGTAAGGCCAGCGGGCGCGGCAGCCGCGTCACCCACCTCCTGGGGTACCCGACGCAGAACGTCAGCCGCTCCCTGCGCCGCAAGTACGCGCCTCCGCCCTGCGGCGGCCCCGAGGACGTGGCCCTAGTGCCCCGCACCGCCTCCGCCTCCTGCGAAGCGGGTCCCTCCCCCGTCTACATCAAGGTCAAGAGCGCGGAGCCGGCCGACTGCGCCGACTGTGCCCAGGTCGAGCAGCGCTCGTGCAAGGACGGCCTCTTAGTGTGAGCGCACAGCACCGGGCTGCGCCCCGGCTGGGAGGTGGTTCGGGGGCTCTCTGCCCGCAGCTGGGGACAGGTTCGGGCCAGCAGACCTGGCTCTCTCATTGGCCACCTAGCGGTGGTAAGGAAATTTCCCTCTGAGAAGCCAAGCCGGGCAGACCCTCCTCCCCTGTAGTGGGAGGAGAGGCGGGGGAGACAGAAAACAGTTCAGAGCTCTCCCTCACCCCTGGTTTCCAGGGAGAGGAAGGGAGAGGAGAGCTGTCGGTATCCCAGAACCGCAGAGGTACAACCCAGATGTCCCCAGCCAAGGCGAGGGCCCCCCAGCCCTGGGTAGGTGGATGTCAGGGCTGAATTGCTCTGTGTGTGAGATCTGAGCTCCAAGGCAACAGTGTTAGCACAATAAAGAAACTTAAAGACTGAAAAAAAAAAAAAA (SEQ IDNO: 71) >NP_808391.2 V-set and immunoglobulin domain-containingprotein 8 precursor [Mus musculus]MGVRGALHLLLVCLSPALLSAVRINGDGQEVMYLAEGDNVRLGCPYLLDPEDLGTNSLDIEWMQVNSEPSHRENVFLTYQDKRIGHGNLPHLQQRVRFAASDPSQYDASINLMNLQVSDTATYECRVKKTTMATRKVIVTVQARPAVPMCWTEGHMSKGNDVVLKCFANGGSQPLSYKWAKISGHSHPYRAGAYHSQHSFHSELSYQESFHSTINQGLGNGDLLLKGINADDDGLYQCTVANHVGYSVCVVEVKVSDSQRVGMIVGAVLGSLLMLACLALGIWGLICCCCGGGGAGGARGAFGYGVGGGVGGGACGDLASEIRVDAEAPGCKASGRGSRVTHLLGYPTQNVSRSLRRKYAPPPCGGPEDVALVPRTASASCEAGPSPVYIKVKSAEPADCADCAQVEQRSCKDGLLV (SEQ ID NO: 72) Human VSIG3>NM_001015887.3 Homo sapiens immunoglobulin superfamily (ISF11)member 11 (IGSF11), transcript variant 2, mRNAAGTCCTGGGGCAGGGCTGGGTGGCACGGCTGGCGAGCCCGGAACGCCTCTGGTCACAGCTCAGCGTCCGCGGAGCCGGGCGGCGCTGCAGCTGCACTTGGCTCGTCTGTGGGTCTGACAGTCCCAGCTCTGCGCGGGGAACAGCGGCCCGGCGCTGGGTGTGGGAGGACCAGGCTGCCCCAAGAGCGCGGAGACTCACGCCCGCTCCTCTCCTGTTGCGACCGGGAGCCGGGTAGGAGGCAGGCGCGCTCCCTGCGGCCCCGGGATGACTTCTCAGCGTTCCCCTCTGGCGCCTTTGCTGCTCCTCTCTCTGCACGGTGTTGCAGCATCCCTGGAAGTGTCAGAGAGCCCTGGGAGTATCCAGGTGGCCCGGGGTCAGCCAGCAGTCCTGCCCTGCACTTTCACTACCAGCGCTGCCCTCATTAACCTCAATGTCATTTGGATGGTCACTCCTCTCTCCAATGCCAACCAACCTGAACAGGTCATCCTGTATCAGGGTGGACAGATGTTTGATGGTGCCCCCCGGTTCCACGGTAGGGTAGGATTTACAGGCACCATGCCAGCTACCAATGTCTCTATCTTCATTAATAACACTCAGTTATCAGACACTGGCACCTACCAGTGCCTGGTCAACAACCTTCCAGACATAGGGGGCAGGAACATTGGGGTCACCGGTCTCACAGTGTTAGTTCCCCCTTCTGCCCCACACTGCCAAATCCAAGGATCCCAGGATATTGGCAGCGATGTCATCCTGCTCTGTAGCTCAGAGGAAGGCATTCCTCGACCAACTTACCTTTGGGAGAAGTTAGACAATACCCTCAAACTACCTCCAACAGCTACTCAGGACCAGGTCCAGGGAACAGTCACCATCCGGAACATCAGTGCCCTGTCTTCAGGTTTGTACCAGTGCGTGGCTTCTAATGCTATTGGAACCAGCACCTGTCTTCTGGATCTCCAGGTTATTTCACCCCAGCCCAGGAACATTGGACTAATAGCTGGAGCCATTGGCACTGGTGCAGTTATTATCATTTTTTGCATTGCACTAATTTTAGGGGCATTCTTTTACTGGAGAAGCAAAAATAAAGAGGAGGAAGAAGAAGAAATTCCTAATGAAATAAGAGAGGATGATCTTCCACCCAAGTGTTCTTCTGCCAAAGCATTTCACACTGAGATTTCCTCCTCGGACAACAACACACTAACCTCTTCCAATGCCTACAACAGTCGATACTGGAGCAACAATCCAAAAGTTCATAGAAACACAGAGTCAGTCAGCCACTTCAGTGACTTGGGCCAATCTTTCTCTTTCCACTCAGGCAATGCCAACATACCATCCATTTATGCTAATGGGACCCATCTGGTCCCGGGTCAACATAAGACTCTGGTAGTGACAGCCAACAGAGGGTCATCACCACAGGTGATGTCCAGGAGCAATGGCTCAGTCAGTAGGAAGCCTCGGCCTCCACACACTCATTCCTACACCATCAGCCACGCAACACTGGAACGAATTGGTGCAGTACCTGTCATGGTACCAGCCCAGAGTCGGGCCGGGTCCTTGGTATAGGACATGAGGAAATGTTGTGTTCAGAAATGAATAAATGGAATGCCCTCATACAAGGGGGAGGGTGGGGTGGGGAGTGCTGGGAAAGAAACACTTCCTTATAATTATATTAGTAAAATGCACAAAGAAGAAGGCAGTGCTGTTACTTGGCCACTAAGATGTGTAAAATGGACTGAAATGCTCCATCATGAAGACTTGCTTCCCCACCAAAGATGTCCTGGGATTCTGCTGGATCTCAAAGATGTGCCAAGCCAAGGAAAAAGATACAAGAGCAGAATAGTACTTAAAATCCAAACTGCCGCCCAGATGGGCTTGTTCTTCATGCCTAACTTAATAATTTTTAAGAGATTAAAGTGCCAGATGGAGTTTAAATATTGAAATTATTTTAAAAGGTAGGTGTCTTTAAGAAAATAACAAGCAACCCTGTGATATGTTCCGTCTCTCCCAATTCCCTCGTTATATAGAGGGCTTAATGGTATAAATGGTTAATATTGGTCCCAACAGGGCTGACTCTTCTATCATATAATCAAAACTTTTTACATGAGCAAAATTCAGTAAGAAATGGGGGAAGACAAAGGAAACGTCTTTGAGAAGCCCCTTCATATTTATTTATTTATCTCTTCCTGAACCATGAATTTCATATGTGGAATATTGCTATATTGACAGATTCTTGCCTGTCTGTGTTATTCTAGGATCTGTTACAGGTCCATGGCAATTACTGTTTATTTTTTCCTGGAAAAATATTTTTTTATAAAAGGCTTTTTTTTTTTTTTAAATACATGAGAGGCATTGGGCTAAGAAAGAAAAGACTGTTGTATAATACCTTGTTCAATGGTTGTATTTAGTGAGCTCATAGAGGTCCATCATATCATGACCGAGCTAGGTTGTGTGGGCAGGAAGGTAGGGCTAAGGGGTTGTAGCCTTGCTGGGCAGCCTCTCAGAGCAAGGTTGTTCAGATCTCCCTTGCTATTACAGTAGGTTACTATTAATGAGGGCAGCACCTGATGCCTTTTGTACTGAGGTATGTAACTTTCTCCTTATTTGACAAGTAGAAGTTAACTTACTTGTCAGGGAGGGCAGACGTTTTTTTGTTCTGTTTCGTTTTTCAAAATAATGCTTTTTGCAAAAGAGGTAAGACTGAGACTAAAGGTGTTATCTTCTGGTGTGCTCCTGGAAGTGTCTACCCTACATTTGTGTCAGCTCAGGGTTGCAGTGTTGCCCAGATGCATTTTACATCACTGTAAAGAGATTACTTTTGTGGTTACTACCTGGCTTGGCTGGCCTTGCGGTTCACCAGATTAATTTACAAACTCCCCCACTTTATTTTGTGCTATGTAGATCTGGCCATACTTGCATTAGTGACTGTCTTGCCTTAACCACACTTAAGCAACCCACAAATTTCTTCTCAGATTTGTTTCCTAGATTACTTATGATACTCATCCCATGTCTCAATAAGAGTGTCTTTTCTTTCTGGATGTGTTCTCTTACTCCCTCTTACCACCATACTTTTTGCTCTCTTCTCCTGCAAGCGTAGTCTTCACAGGGAGTGGCTTCCTGACATTTTTTTCAGTTATGTGAATGAATGGAAACCAACAGCTGCTGCAAACACTGTTTTTCCAAGAAGGCTACACTCAGAACCTAACCATTGCCAACCATTTCAGTATTGATAAAAAGCTGAATTTACTTTAGCATTACTTATTTTTTTTTCCATTTGATGGTTCTTACTTTGTAAAAATTTAAATAAATGAATGTCTATACTTTTTATAAAGAAAAGTGAAAATACCATGACACTGAAAAGATGATGCTATCAGATGCTGTTTAGAAAGCATTTATCTTGCATTTCTTTATTCTTTCTAATTATCTAAAATTCAATAAAATTTTATTCATATAAAATAAGTTGTCATTAATTATCAATACTAACGAGTATGTCATTTTAAAACTTAGTATTCTCTTTAATGTTACAAGA (SEQ IDNO: 73) >NP_001015887.1 immunoglobulin superfamily member 11isoform b precursor [Homo sapiens]MTSQRSPLAPLLLLSLHGVAASLEVSESPGSIQVARGQPAVLPCTFTTSAALINLNVIWMVTPLSNANQPEQVILYQGGQMFDGAPRFHGRVGFTGTMPATNVSIFINNTQLSDTGTYQCLVNNLPDIGGRNIGVTGLTVLVPPSAPHCQIQGSQDIGSDVILLCSSEEGIPRPTYLWEKLDNTLKLPPTATQDQVQGTVTIRNISALSSGLYQCVASNAIGTSTCLLDLQVISPQPRNIGLIAGAIGTGAVIIIFCIALILGAFFYWRSKNKEEEEEEIPNEIREDDLPPKCSSAKAFHTEISSSDNNTLTSSNAYNSRYWSNNPKVHRNTESVSHFSDLGQSFSFHSGNANIPSIYANGTHLVPGQHKTLVVTANRGSSPQVMSRSNGSVSRKPRPPHTHSYTISHATLERIGAVPVMVPAQSRAGSLV (SEQ ID NO: 74) Mouse VSIG3>NM_170599.2 Mus musculus immunoglobulin superfamily, (IGSF11)member 11 (Igsf11), mRNACGGCTGGTGGTGGCCGCGGCGGCCGGCGAGCCCGGGACGCCCGAGCCTGCCCCGAGCCTCGGCGGAGCGGAGTGGCCTCGGCGCTCCCGTGTCCCGCTTGGTCCCACGCTGCACCCCGCCGCCCAGGAGCCCGGCGGACGGCGGCTCCCCCGGCGGCTCCGGCATGACTCGGCGGCGCTCCGCTCCGGCGTCCTGGCTGCTCGTGTCGCTGCTCGGTGTCGCAACATCCCTGGAAGTGTCCGAGAGCCCAGGCAGTGTCCAGGTGGCCCGGGGCCAGACAGCAGTCCTGCCCTGCGCCTTCTCCACCAGTGCTGCCCTCCTGAACCTCAATGTCATTTGGATGGTCATTCCCCTCTCCAATGCAAACCAGCCCGAACAGGTCATTCTTTATCAGGGTGGACAAATGTTTGACGGCGCCCTCCGGTTCCACGGGAGGGTAGGATTTACCGGCACCATGCCTGCTACCAATGTCTCGATCTTCATCAATAACACACAGCTGTCAGATACGGGCACGTACCAGTGCTTGGTGAATAACCTTCCAGACAGAGGGGGCAGAAACATCGGGGTCACTGGCCTCACAGTGTTAGTCCCCCCTTCTGCTCCACAATGCCAAATCCAAGGATCCCAGGACCTCGGCAGTGACGTCATCCTTCTGTGTAGTTCAGAGGAAGGCATCCCTCGGCCCACGTACCTTTGGGAGAAGTTAGATAATACGCTCAAGCTACCTCCAACAGCCACTCAGGACCAGGTCCAGGGAACAGTCACCATCCGGAATATCAGTGCCCTCTCTTCCGGTCTGTACCAGTGTGTGGCTTCTAATGCCATCGGGACCAGCACCTGTCTGCTGGACCTCCAGGTTATCTCACCCCAGCCCCGGAGCGTTGGAGTAATAGCCGGAGCGGTTGGCACCGGTGCTGTTCTTATCGTCATCTGCCTTGCACTAATTTCAGGGGCGTTCTTTTACTGGAGAAGCAAAAACAAAGAGGAGGAGGAGGAAGAAATTCCTAATGAAATCAGAGAGGATGATCTTCCCCCTAAATGCTCTTCTGCCAAAGCCTTCCACACGGAGATATCCTCCTCAGAAAATAACACGCTGACCTCTTCCAATACCTACAACAGTCGATACTGGAACAACAATCCAAAACCCCATAGAAACACAGAGTCTTTCAACCACTTCAGTGACTTACGCCAGTCTTTCTCTGGCAATGCAGTTATCCCATCAATCTATGCAAATGGGAACCATCTGGTTTTGGGTCCACATAAGACTCTGGTAGTTACAGCCAACAGAGGGTCATCACCTCAGGTCTTGCCCAGGAACAATGGTTCAGTCAGCAGGAAGCCTTGGCCTCAACACACTCATTCCTACACAGTAAGCCAAATGACCCTGGAGCGCATCGGTGCAGTGCCTGTCATGGTGCCTGCCCAGAGTCGAGCAGGGTCCCTGGTATAGGATGACTGAGGAAACCATGTTCAGAAGAGAATAAATGGACCGCCTTCAGGCAAGGGGGGAGCACTGCCTTCAGGCAAGGGGGGAGCACTGCCTTCAGGCAAGAGGGAGAGTGGGATGGGTGAGTGCTGAAAAATAAACTTTTGTTACGATTCCATTAGCAAAAAGCACAAAGAGGAGGCGTGTGTGAAGTGGCCTGGGGTTGTTCCATAATGAAGACTCAAGAAGACTGTTTCCCCACCACAGATGTCCTGAGATTCAGTTAAAACGAAACATGCTGCATCTCCAGAGATGTGCCAAGCCAAGGAGAATGCTAGAAGCAGAGTAAAGCTTACCCCCCAAACTGTGGTCCAGCTGGACCCCTTCTTTAATTCTTGCCTAACTTAATTATTTTCAGGACCCTTCAAGTGCCAGGTGGAATTTACATAATGAAATTATTTTTTAAAAATAGGTGTCCTTAGGGAGAGAAAACAGGAGCAAGCTCATGGTCTGGCCTAGTCTCCCTCTCCCACTCCTTCTGATGACACTAGCAATGCATTCCATCTGACCTGACTTTATCATAGAGGCAAAATTGTTCAGAACACTGGCTGGAGATGGGGAGAAATAAGGAAACTTCTTGTGAACACCCTACACACACACACACACACACACACACACACACACACACACACACACACACACACACACACACATTTATTTACCTCCTCCTGAACCATGAATCGTATTGGTGATTTTGCTATATTGACAGATTCTCATCTGTTACACTCTAGGATCTCTCACAGGTCTGTGGCAATTACTGTTCATGATTTCCTGAAAAAATATTTTTTTAAAAGAAAACTATTTTTTTTAAATACTAGAGAGACAGTGGACTAGGAAAGCGAGAACTTGCCGCCTTGTCTAGTGACTGTATTCAATGACTGAACAGAGGCCCCCCCCACCATACAAGAGTTTTAGGTGATTGAGTGGGTGGAACCAGCTGGAGCCAGGTGGGAGGGGCCTTTACATTGCCAGCAGGGCCCCAAAGAATTGAGATTGTGTATGGCAACCGTTAATGAGGACAGCGCCTGATGCCTTTTGTACCGAGGAAGATAATTGCCTCTTGTTTGACAAGTAGAGTTTAGTAGGTTATTACAAAAAGGGCAAGAGTTGTTTTGGTTTTGTTTCTTTCAAAATAATTTTTTTTCAAAAGAATAACAAGGGTTAGGCAAATGGGGGACCTTCCTGTGTGCTCTTGGGGGTCTGCTCAGCATCTGGAAATTTGGGTGTGCGATTTTCCCTGAACACATTGCATACCAGTGTAAAAAGACTCTGCCTCCCCCCTTTTTGGCTTTTTTACTGGGCTTGGCTGGCCTTGCAGTTTACCAGATTCATTTACAGACTCTCTGCTCTGTATGGCGCCGCCTGCCATGTCTGTCTTGGTGACTATCCTGCCTTAATCACTTTGCTTTAGGGCAACTCATGGTGATCTCTTCCAAGATCTGTTTTTAAATTGTTTGGACTACTTGAGCCACAACTCTCAGAGGACATTCCTTTTTTTTTTTTTTTTTTTTTCTCCTTTCTTCCATTGCTTTGTCCCTCTTCCCCTGTGCTTCCTGCCTTCTTTCCCTGTCCCATGGGCACAGTCCTCACAGGGAGTGGCCTCCTCTCTCCAGTGATGTAAGTGAATGGAAGCCATCACTGGCTGCACATACCTTTTTCAAAAGGGACACTCGGGAAGTCACTGCTGTGACCGTTTCGATGTTGATAAGAAGGTGAATTTACTGTAGTGTTACCACCTTCTCCCCACTTGATGGTTCTTGACTTTGTAAAAATTTAAATAAATGAATGTCTATACTTTTTAAGGAAAAGAGAAAATACCATGTCACAGAAAAGGTGAAACTATTAGATGCTGTTTAGAAAGCATTTATCTTGCATTTCTTTATTCTTTCTAATTACCTAAAATTCAATAAAAGTTTATTCATATAAAAAAAAAAAAAAAAAAAA (SEQ ID NO: 75) >NP_733548.2 immunoglobulin superfamily member 11precursor [Mus musculus]MTRRRSAPASWLLVSLLGVATSLEVSESPGSVQVARGQTAVLPCAFSTSAALLNLNVIWMVIPLSNANQPEQVILYQGGQMFDGALRFHGRVGFTGTMPATNVSIFINNTQLSDTGTYQCLVNNLPDRGGRNIGVTGLTVLVPPSAPQCQIQGSQDLGSDVILLCSSEEGIPRPTYLWEKLDNTLKLPPTATQDQVQGTVTIRNISALSSGLYQCVASNAIGTSTCLLDLQVISPQPRSVGVIAGAVGTGAVLIVICLALISGAFFYWRSKNKEEEEEEIPNEIREDDLPPKCSSAKAFHTEISSSENNTLTSSNTYNSRYWNNNPKPHRNTESFNHFSDLRQSFSGNAVIPSIYANGNHLVLGPHKTLVVTANRGSSPQVLPRNNGSVSRKPWPQHTHSYTVSQMTLERIGAVPVMVPAQSRAGSLV (SEQ ID NO: 76) Human VSIG4>NM_007268.3 Homo sapiens V-set and immunoglobulin domaincontaining 4 (VSIG4), transcript variant 1, mRNAACAGACGCTGGCGGCCACCAGAAGTTTGAGCCTCTTTGGTAGCAGGAGGCTGGAAGAAAGGACAGAAGTAGCTCTGGCTGTGATGGGGATCTTACTGGGCCTGCTACTCCTGGGGCACCTAACAGTGGACACTTATGGCCGTCCCATCCTGGAAGTGCCAGAGAGTGTAACAGGACCTTGGAAAGGGGATGTGAATCTTCCCTGCACCTATGACCCCCTGCAAGGCTACACCCAAGTCTTGGTGAAGTGGCTGGTACAACGTGGCTCAGACCCTGTCACCATCTTTCTACGTGACTCTTCTGGAGACCATATCCAGCAGGCAAAGTACCAGGGCCGCCTGCATGTGAGCCACAAGGTTCCAGGAGATGTATCCCTCCAATTGAGCACCCTGGAGATGGATGACCGGAGCCACTACACGTGTGAAGTCACCTGGCAGACTCCTGATGGCAACCAAGTCGTGAGAGATAAGATTACTGAGCTCCGTGTCCAGAAACTCTCTGTCTCCAAGCCCACAGTGACAACTGGCAGCGGTTATGGCTTCACGGTGCCCCAGGGAATGAGGATTAGCCTTCAATGCCAGGCTCGGGGTTCTCCTCCCATCAGTTATATTTGGTATAAGCAACAGACTAATAACCAGGAACCCATCAAAGTAGCAACCCTAAGTACCTTACTCTTCAAGCCTGCGGTGATAGCCGACTCAGGCTCCTATTTCTGCACTGCCAAGGGCCAGGTTGGCTCTGAGCAGCACAGCGACATTGTGAAGTTTGTGGTCAAAGACTCCTCAAAGCTACTCAAGACCAAGACTGAGGCACCTACAACCATGACATACCCCTTGAAAGCAACATCTACAGTGAAGCAGTCCTGGGACTGGACCACTGACATGGATGGCTACCTTGGAGAGACCAGTGCTGGGCCAGGAAAGAGCCTGCCTGTCTTTGCCATCATCCTCATCATCTCCTTGTGCTGTATGGTGGTTTTTACCATGGCCTATATCATGCTCTGTCGGAAGACATCCCAACAAGAGCATGTCTACGAAGCAGCCAGGGCACATGCCAGAGAGGCCAACGACTCTGGAGAAACCATGAGGGTGGCCATCTTCGCAAGTGGCTGCTCCAGTGATGAGCCAACTTCCCAGAATCTGGGCAACAACTACTCTGATGAGCCCTGCATAGGACAGGAGTACCAGATCATCGCCCAGATCAATGGCAACTACGCCCGCCTGCTGGACACAGTTCCTCTGGATTATGAGTTTCTGGCCACTGAGGGCAAAAGTGTCTGTTAAAAATGCCCCATTAGGCCAGGATCTGCTGACATAATTGCCTAGTCAGTCCTTGCCTTCTGCATGGCCTTCTTCCCTGCTACCTCTCTTCCTGGATAGCCCAAAGTGTCCGCCTACCAACACTGGAGCCGCTGGGAGTCACTGGCTTTGCCCTGGAATTTGCCAGATGCATCTCAAGTAAGCCAGCTGCTGGATTTGGCTCTGGGCCCTTCTAGTATCTCTGCCGGGGGCTTCTGGTACTCCTCTCTAAATACCAGAGGGAAGATGCCCATAGCACTAGGACTTGGTCATCATGCCTACAGACACTATTCAACTTTGGCATCTTGCCACCAGAAGACCCGAGGGAGGCTCAGCTCTGCCAGCTCAGAGGACCAGCTATATCCAGGATCATTTCTCTTTCTTCAGGGCCAGACAGCTTTTAATTGAAATTGTTATTTCACAGGCCAGGGTTCAGTTCTGCTCCTCCACTATAAGTCTAATGTTCTGACTCTCTCCTGGTGCTCAATAAATATCTAATCATAACAGCAA (SEQ ID NO: 77) >NP_009199.1 V-set and immunoglobulin domain-containingprotein 4 isoform 1 precursor [Homo sapiens]MGILLGLLLLGHLTVDTYGRPILEVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWLVQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHKVPGDVSLQLSTLEMDDRSHYTCEVTWQTPDGNQVVRDKITELRVQKLSVSKPTVTTGSGYGFTVPQGMRISLQCQARGSPPISYIWYKQQTNNQEPIKVATLSTLLFKPAVIADSGSYFCTAKGQVGSEQHSDIVKFVVKDSSKLLKTKTEAPTTMTYPLKATSTVKQSWDWTTDMDGYLGETSAGPGKSLPVFAIILIISLCCMVVFTMAYIMLCRKTSQQEHVYEAARAHAREANDSGETMRVAIFASGCSSDEPTSQNLGNNYSDEPCIGQEYQIIAQINGNYARLLDTVPLDYEFLATEGKSVC(SEQ ID NO: 78) Mouse VSIG4>NM_177789.5 Mus musculus V-set and immunoglobulin domaincontaining 4 (Vsig4), mRNAAGCTACCAGCACTTCCAGGTTCTTCAGCAGCAAGAGGATGGAAGGATGAATAGAAGTAGCTTCAAATAGGATGGAGATCTCATCAGGCTTGCTGTTCCTGGGCCACCTAATAGTGCTCACCTATGGCCACCCCACCCTAAAAACACCTGAGAGTGTGACAGGGACCTGGAAAGGAGATGTGAAGATTCAGTGCATCTATGATCCCCTGAGAGGCTACAGGCAAGTTTTGGTGAAATGGCTGGTAAGACACGGCTCTGACTCCGTCACCATCTTCCTACGTGACTCCACTGGAGACCATATCCAGCAGGCAAAGTACAGAGGCCGCCTGAAAGTGAGCCACAAAGTTCCAGGAGATGTGTCCCTCCAAATAAATACCCTGCAGATGGATGACAGGAATCACTATACATGTGAGGTCACCTGGCAGACTCCTGATGGAAACCAAGTAATAAGAGATAAGATCATTGAGCTCCGTGTTCGGAAATATAATCCACCTAGAATCAATACTGAAGCACCTACAACCCTGCACTCCTCTTTGGAAGCAACAACTATAATGAGTTCAACCTCTGACTTGACCACTAATGGGACTGGAAAACTTGAGGAGACCATTGCTGGTTCAGGGAGGAACCTGCCAATCTTTGCCATAATCTTCATCATCTCCCTTTGCTGCATAGTAGCTGTCACCATACCTTATATCTTGTTCCGCTGCAGGACATTCCAACAAGAGTATGTCTATGGAGTGAGCAGGGTGTTTGCCAGGAAGACAAGCAACTCTGAAGAAACCACAAGGGTGACTACCATCGCAACTGATGAACCAGATTCCCAGGCTCTGATTAGTGACTACTCTGATGATCCTTGCCTCAGCCAGGAGTACCAAATAACCATCAGATCAACAATGTCTATTCCTGCCTGCTGAACACAGTTTCCAGAAACTAAGAAGTTCTTGCTACTGAAGAAAATAACATCTGCTAAAATGCCCCTACTAAGTCAAGGTCTACTGGCGTAATTACCTGTTACTTATTTACTACTTGCCTTCAACATAGCTTTCTCCCTGGCTTCCTTTCTTCTTAGACAACCTAAAGTATCTATCTAGTCTGCCAATTCTGGGGCCATTGAGAAATCCTGGGTTTGGCTAAGAATATACTACATGCACCTCAAGAAATCTAGCTTCTGGGCTTCACCCAGAACAATTTTCTTCCTAGGGCCTTCACAACTCTTCTCCAAACAGCAGAGAAATTCCATAGCAGTAGAGGTTCTTTATCATGCCTCCAGACAGCGTGAGTCTCAGTCCTACAAACTCAGACAAGCACATGGGTCTAGGATTACTCCTCTTTCTCTAGGGCCAGATGACTTTTAATTGATATTACTATTGCTACATTATGAATCTAATGCACATGTATTCTTTTGTTGTTAATAAATGTTTAATCATGACATCAA(SEQ ID NO: 79) >NP_808457.1 V-set and immunoglobulin domain-containingprotein 4 precursor [Mus musculus]MEISSGLLFLGHLIVLTYGHPTLKTPESVTGTWKGDVKIQCIYDPLRGYRQVLVKWLVRHGSDSVTIFLRDSTGDHIQQAKYRGRLKVSHKVPGDVSLQINTLQMDDRNHYTCEVTWQTPDGNQVIRDKIIELRVRKYNPPRINTEAPTTLHSSLEATTIMSSTSDLTTNGTGKLEETIAGSGRNLPIFAIIFIISLCCIVAVTIPYILFRCRTFQQEYVYGVSRVFARKTSNSEETTRVTTIATDEPDSQALISDYSDDPCLSQEYQITIRSTMSIPAC (SEQ ID NO: 80)Human Tim-3 >NM_032782.5 Homo sapiens hepatitis A virus cellular(HAVCR2) receptor 2 (HAVCR2) , mRNAATTTGGAGAGTTAAAACTGTGCCTAACAGAGGTGTCCTCTGACTTTTCTTCTGCAAGCTCCATGTTTTCACATCTTCCCTTTGACTGTGTCCTGCTGCTGCTGCTGCTACTACTTACAAGGTCCTCAGAAGTGGAATACAGAGCGGAGGTCGGTCAGAATGCCTATCTGCCCTGCTTCTACACCCCAGCCGCCCCAGGGAACCTCGTGCCCGTCTGCTGGGGCAAAGGAGCCTGTCCTGTGTTTGAATGTGGCAACGTGGTGCTCAGGACTGATGAAAGGGATGTGAATTATTGGACATCCAGATACTGGCTAAATGGGGATTTCCGCAAAGGAGATGTGTCCCTGACCATAGAGAATGTGACTCTAGCAGACAGTGGGATCTACTGCTGCCGGATCCAAATCCCAGGCATAATGAATGATGAAAAATTTAACCTGAAGTTGGTCATCAAACCAGCCAAGGTCACCCCTGCACCGACTCGGCAGAGAGACTTCACTGCAGCCTTTCCAAGGATGCTTACCACCAGGGGACATGGCCCAGCAGAGACACAGACACTGGGGAGCCTCCCTGATATAAATCTAACACAAATATCCACATTGGCCAATGAGTTACGGGACTCTAGATTGGCCAATGACTTACGGGACTCTGGAGCAACCATCAGAATAGGCATCTACATCGGAGCAGGGATCTGTGCTGGGCTGGCTCTGGCTCTTATCTTCGGCGCTTTAATTTTCAAATGGTATTCTCATAGCAAAGAGAAGATACAGAATTTAAGCCTCATCTCTTTGGCCAACCTCCCTCCCTCAGGATTGGCAAATGCAGTAGCAGAGGGAATTCGCTCAGAAGAAAACATCTATACCATTGAAGAGAACGTATATGAAGTGGAGGAGCCCAATGAGTATTATTGCTATGTCAGCAGCAGGCAGCAACCCTCACAACCTTTGGGTTGTCGCTTTGCAATGCCATAGATCCAACCACCTTATTTTTGAGCTTGGTGTTTTGTCTTTTTCAGAAACTATGAGCTGTGTCACCTGACTGGTTTTGGAGGTTCTGTCCACTGCTATGGAGCAGAGTTTTCCCATTTTCAGAAGATAATGACTCACATGGGAATTGAACTGGGACCTGCACTGAACTTAAACAGGCATGTCATTGCCTCTGTATTTAAGCCAACAGAGTTACCCAACCCAGAGACTGTTAATCATGGATGTTAGAGCTCAAACGGGCTTTTATATACACTAGGAATTCTTGACGTGGGGTCTCTGGAGCTCCAGGAAATTCGGGCACATCATATGTCCATGAAACTTCAGATAAACTAGGGAAAACTGGGTGCTGAGGTGAAAGCATAACTTTTTTGGCACAGAAAGTCTAAAGGGGCCACTGATTTTCAAAGAGATCTGTGATCCCTTTTTGTTTTTTGTTTTTGAGATGGAGTCTTGCTCTGTTGCCCAGGCTGGAGTGCAATGGCACAATCTCGGCTCACTGCAAGCTCCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCTGAGTGGCTGGGATTACAGGCATGCACCACCATGCCCAGCTAATTTGTTGTATTTTTAGTAGAGACAGGGTTTCACCATGTTGGCCAGTGTGGTCTCAAACTCCTGACCTCATGATTTGCCTGCCTCGGCCTCCCAAAGCACTGGGATTACAGGCGTGAGCCACCACATCCAGCCAGTGATCCTTAAAAGATTAAGAGATGACTGGACCAGGTCTACCTTGATCTTGAAGATTCCCTTGGAATGTTGAGATTTAGGCTTATTTGAGCACTGCCTGCCCAACTGTCAGTGCCAGTGCATAGCCCTTCTTTTGTCTCCCTTATGAAGACTGCCCTGCAGGGCTGAGATGTGGCAGGAGCTCCCAGGGAAAAACGAAGTGCATTTGATTGGTGTGTATTGGCCAAGTTTTGCTTGTTGTGTGCTTGAAAGAAAATATCTCTGACCAACTTCTGTATTCGTGGACCAAACTGAAGCTATATTTTTCACAGAAGAAGAAGCAGTGACGGGGACACAAATTCTGTTGCCTGGTGGAAAGAAGGCAAAGGCCTTCAGCAATCTATATTACCAGCGCTGGATCCTTTGACAGAGAGTGGTCCCTAAACTTAAATTTCAAGACGGTATAGGCTTGATCTGTCTTGCTTATTGTTGCCCCCTGCGCCTAGCACAATTCTGACACACAATTGGAACTTACTAAAAATTTTTTTTTACTGTT (SEQ ID NO: 81) >NP_116171.3 hepatitis A virus cellular receptor 2precursor [Homo sapiens]MFSHLPFDCVLLLLLLLLTRSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIGIYIGAGICAGLALALIFGALIFKWYSHSKEKIQNLSLISLANLPPSGLANAVAEGIRSEENIYTIEENVYEVEEPNEYYCYVSSRQQPSQPLGCRFAMP (SEQ ID NO: 82) Mouse Tim-3>NM_134250.2 Mus musculus hepatitis A virus cellular (HAVCR2)receptor 2 (Havcr2), mRNAACCATTTTAACCGAGGAGCTAAAGCTATCCCTACACAGAGCTGTCCTTGGATTTCCCCTGCCAAGTACTCATGTTTTCAGGTCTTACCCTCAACTGTGTCCTGCTGCTGCTGCAACTACTACTTGCAAGGTCATTGGAAAATGCTTATGTGTTTGAGGTTGGTAAGAATGCCTATCTGCCCTGCAGTTACACTCTATCTACACCTGGGGCACTTGTGCCTATGTGCTGGGGCAAGGGATTCTGTCCTTGGTCACAGTGTACCAACGAGTTGCTCAGAACTGATGAAAGAAATGTGACATATCAGAAATCCAGCAGATACCAGCTAAAGGGCGATCTCAACAAAGGAGACGTGTCTCTGATCATAAAGAATGTGACTCTGGATGACCATGGGACCTACTGCTGCAGGATACAGTTCCCTGGTCTTATGAATGATAAAAAATTAGAACTGAAATTAGACATCAAAGCAGCCAAGGTCACTCCAGCTCAGACTGCCCATGGGGACTCTACTACAGCTTCTCCAAGAACCCTAACCACGGAGAGAAATGGTTCAGAGACACAGACACTGGTGACCCTCCATAATAACAATGGAACAAAAATTTCCACATGGGCTGATGAAATTAAGGACTCTGGAGAAACGATCAGAACTGCTATCCACATTGGAGTGGGAGTCTCTGCTGGGTTGACCCTGGCACTTATCATTGGTGTCTTAATCCTTAAATGGTATTCCTGTAAGAAAAAGAAGTTATCGAGTTTGAGCCTTATTACACTGGCCAACTTGCCTCCAGGAGGGTTGGCAAATGCAGGAGCAGTCAGGATTCGCTCTGAGGAAAATATCTACACCATCGAGGAGAACGTATATGAAGTGGAGAATTCAAATGAGTACTACTGCTACGTCAACAGCCAGCAGCCATCCTGACCGCCTCTGGACTGCCACTTTTAAAGGCTCGCCTTCATTTCTGACTTTGGTATTTCCCTTTTTGAAAACTATGTGATATGTCACTTGGCAACCTCATTGGAGGTTCTGACCACAGCCACTGAGAAAAGAGTTCCAGTTTTCTGGGGATAATTAACTCACAAGGGGATTCGACTGTAACTCATGCTACATTGAAATGCTCCATTTTATCCCTGAGTTTCAGGGATCGGATCTCCCACTCCAGAGACTTCAATCATGCGTGTTGAAGCTCACTCGTGCTTTCATACATTAGGAATGGTTAGTGTGATGTCTTTGAGACATAGAGGTTTGTGGTATATCTGCAAAGCTCCTGAACAGGTAGGGGGAATAAAGGGCTAAGATAGGAAGGTGAGGTTCTTTGTTGATGTTGAAAATCTAAAGAAGTTGGTAGCTTTTCTAGAGATTTCTGACCTTGAAAGATTAAGAAAAAGCCAGGTGGCATATGCTTAACACTATATAACTTGGGAACCTTAGGCAGGAGGGTGATAAGTTCAAGGTCAGCCAGGGCTATGCTGGTAAGACTGTCTCAAAATCCAAAGACGAAAATAAACATAGAGACAGCAGGAGGCTGGAGATGAGGCTCGGACAGTGAGGTGCATTTTGTACAAGCACGAGGAATCTATATTTGATCGTAGACCCCACATGAAAAAGCTAGGCCTGGTAGAGCATGCTTGTAGACTCAAGAGATGGAGAGGTAAAGGCACAACAGATCCCCGGGGCTTGCGTGCAGTCAGCTTAGCCTAGGTGCTGAGTTCCAAGTCCACAAGAGTCCCTGTCTCAAAGTAAGATGGACTGAGTATCTGGCGAATGTCCATGGGGGTTGTCCTCTGCTCTCAGAAGAGACATGCACATGAACCTGCACACACACACACACACACACACACACACACACACACACACACACACACACACACATGAAATGAAGGTTCTCTCTGTGCCTGCTACCTCTCTATAACATGTATCTCTACAGGACTCTCCTCTGCCTCTGTTAAGACATGAGTGGGAGCATGGCAGAGCAGTCCAGTAATTAATTCCAGCACTCAGAAGGCTGGAGCAGAAGCGTGGAGAGTTCAGGAGCACTGTGCCCAACACTGCCAGACTCTTCTTACAGAAGAAAAAGGTTACCCGCAAGCAGCCTGCTGTCTGTAAAAGGAAACCCTGCGAAAGGCAAACTTTGACTGTTGTGTGCTCAAGGGGAACTGACTCAGACAACTTCTCCATTCCTGGAGGAAACTGGAGCTGTTTCTGACAGAAGAACAACCGGTGACTGGGACATACGAAGGCAGAGCTCTTGCAGCAATCTATATAGTCAGCAAAATATTCTTTGGGAGGACAGTCGTCACCAAATTGATTTCCAAGCCGGTGGACCTCAGTTTCATCTGGCTTACAGCTGCCTGCCCAGTGCCCTTGATCTGTGCTGGCTCCCATCTATAACAGAATCAAATTAAATAGACCCCGAGTGAAAATATTAAGTGAGCAGAAAGGTAGCTTTGTTCAAAGATTTTTTTGCATTGGGGAGCAACTGTGTACATCAGAGGACATCTGTTAGTGAGGACACCAAAACCTGTGGTACCGTTTTTTCATGTATGAATTTTGTTGTTTAGGTTGCTTCTAGCTAGCTGTGGAGGTCCTGGCTTTCTTAGGTGGGTATGGAAGGGAGACCATCTAACAAAATCCATTAGAGATAACAGCTCTCATGCAGAAGGGAAAACTAATCTCAAATGTTTTAAAGTAATAAAACTGTACTGGCAAAGTACTTTGAGCATATTTAAA (SEQ IDNO: 83) >NP_599011.2 hepatitis A virus cellular receptor 2homolog precursor [Mus musculus]MFSGLTLNCVLLLLQLLLARSLENAYVFEVGKNAYLPCSYTLSTPGALVPMCWGKGFCPWSQCTNELLRTDERNVTYQKSSRYQLKGDLNKGDVSLIIKNVTLDDHGTYCCRIQFPGLMNDKKLELKLDIKAAKVTPAQTAHGDSTTASPRTLTTERNGSETQTLVTLHNNNGTKISTWADEIKDSGETIRTAIHIGVGVSAGLTLALIIGVLILKWYSCKKKKLSSLSLITLANLPPGGLANAGAVRIRSEENIYTIEENVYEVENSNEYYCYVNSQQPS (SEQ ID NO: 84)Human Tim-4 >NM_138379.3 Homo sapiens T cell immunoglobulin and mucin(TIMD4) domain containing 4 (TIMD4), transcript variant 1, mRNAAGACTCCTGGGTCCGGTCAACCGTCAAAATGTCCAAAGAACCTCTCATTCTCTGGCTGATGATTGAGTTTTGGTGGCTTTACCTGACACCAGTCACTTCAGAGACTGTTGTGACGGAGGTTTTGGGTCACCGGGTGACTTTGCCCTGTCTGTACTCATCCTGGTCTCACAACAGCAACAGCATGTGCTGGGGGAAAGACCAGTGCCCCTACTCCGGTTGCAAGGAGGCGCTCATCCGCACTGATGGAATGAGGGTGACCTCAAGAAAGTCAGCAAAATATAGACTTCAGGGGACTATCCCGAGAGGTGATGTCTCCTTGACCATCTTAAACCCCAGTGAAAGTGACAGCGGTGTGTACTGCTGCCGCATAGAAGTGCCTGGCTGGTTCAACGATGTAAAGATAAACGTGCGCCTGAATCTACAGAGAGCCTCAACAACCACGCACAGAACAGCAACCACCACCACACGCAGAACAACAACAACAAGCCCCACCACCACCCGACAAATGACAACAACCCCAGCTGCACTTCCAACAACAGTCGTGACCACACCCGATCTCACAACCGGAACACCACTCCAGATGACAACCATTGCCGTCTTCACAACAGCAAACACGTGCCTTTCACTAACCCCAAGCACCCTTCCGGAGGAAGCCACAGGTCTTCTGACTCCCGAGCCTTCTAAGGAAGGGCCCATCCTCACTGCAGAATCAGAAACTGTCCTCCCCAGTGATTCCTGGAGTAGTGTTGAGTCTACTTCTGCTGACACTGTCCTGCTGACATCCAAAGAGTCCAAAGTTTGGGATCTCCCATCAACATCCCACGTGTCAATGTGGAAAACGAGTGATTCTGTGTCTTCTCCTCAGCCTGGAGCATCTGATACAGCAGTTCCTGAGCAGAACAAAACAACAAAAACAGGACAGATGGATGGAATACCCATGTCAATGAAGAATGAAATGCCCATCTCCCAACTACTGATGATCATCGCCCCCTCCTTGGGATTTGTGCTCTTCGCATTGTTTGTGGCGTTTCTCCTGAGAGGGAAACTCATGGAAACCTATTGTTCGCAGAAACACACAAGGCTAGACTACATTGGAGATAGTAAAAATGTCCTCAATGACGTGCAGCATGGAAGGGAAGACGAAGACGGCCTTTTTACCCTCTAACAACGCAGTAGCATGTTAGATTGAGGATGGGGGCATGACACTCCAGTGTCAAAATAAGTCTTAGTAGATTTCCTTGTTTCATAAAAAAGACTCACTTATTCCATGGATGTCATTGATCCAGGCTTGCTTTAGTTTCATGAATGAAGGGTACTTTAGAGACCACAA (SEQ ID NO: 85) >NP_612388.2 T-cell immunoglobulin and mucin domain-containing protein 4 isoform 1 precursor [Homo sapiens]MSKEPLILWLMIEFWWLYLTPVTSETVVTEVLGHRVTLPCLYSSWSHNSNSMCWGKDQCPYSGCKEALIRTDGMRVTSRKSAKYRLQGTIPRGDVSLTILNPSESDSGVYCCRIEVPGWFNDVKINVRLNLQRASTTTHRTATTTTRRTTTTSPTTTRQMTTTPAALPTTVVTTPDLTTGTPLQMTTIAVFTTANTCLSLTPSTLPEEATGLLTPEPSKEGPILTAESETVLPSDSWSSVESTSADTVLLTSKESKVWDLPSTSHVSMWKTSDSVSSPQPGASDTAVPEQNKTTKTGQMDGIPMSMKNEMPISQLLMIIAPSLGFVLFALFVAFLLRGKLMETYCSQKHTRLDYIGDSKNVLNDVQHGREDEDGLFTL (SEQ ID NO: 86) Mouse Tim-4>NM_178759.4 Mus musculus T cell immunoglobulin and mucin (TIMD4)domain containing 4 (Timd4), mRNAAGATCCTATCAAAATGTCCAAGGGGCTTCTCCTCCTCTGGCTGGTGACGGAGCTCTGGTGGCTTTATCTGACACCAGCTGCCTCAGAGGATACAATAATAGGGTTTTTGGGCCAGCCGGTGACTTTGCCTTGTCATTACCTCTCGTGGTCCCAGAGCCGCAACAGTATGTGCTGGGGCAAAGGTTCATGTCCCAATTCCAAGTGCAATGCAGAGCTTCTCCGTACAGATGGAACAAGAATCATCTCCAGGAAGTCAACAAAATATACACTTTTGGGGAAGGTCCAGTTTGGTGAAGTGTCCTTGACCATCTCAAACACCAATCGAGGTGACAGTGGGGTGTACTGCTGCCGTATAGAGGTGCCTGGCTGGTTCAATGATGTCAAGAAGAATGTGCGCTTGGAGCTGAGGAGAGCCACAACAACCAAAAAACCAACAACAACCACCCGGCCAACCACCACCCCTTATGTGACCACCACCACCCCAGAGCTGCTTCCAACAACAGTCATGACCACATCTGTTCTCCCAACCACCACACCACCCCAGACACTAGCCACCACTGCCTTCAGTACAGCAGTGACCACGTGCCCCTCAACAACACCTGGCTCCTTCTCACAAGAAACCACAAAAGGGTCCGCCTTCACTACAGAATCAGAAACTCTGCCTGCATCCAATCACTCTCAAAGAAGCATGATGACCATATCTACAGACATAGCCGTACTCAGGCCCACAGGCTCTAACCCTGGGATTCTCCCATCCACTTCACAGCTGACGACACAGAAAACAACATTAACAACAAGTGAGTCTTTGCAGAAGACAACTAAATCACATCAGATCAACAGCAGACAGACCATCTTGATCATTGCCTGCTGTGTGGGATTTGTGCTAATGGTGTTATTGTTTCTGGCGTTTCTCCTTCGAGGGAAAGTCACAGGAGCCAACTGTTTGCAGAGACACAAGAGGCCAGACAACACTGAAGATAGTGACAGCGTCCTCAATGACATGTCACACGGGAGGGATGATGAAGACGGGATCTTCACTCTCTGACTCACCATCTTTATTTAGGATTAAGGATAGGGAATGGCACTTGAATTGTCAAAATAAGTTTGGGGACATTGTAATTTCCGTTTAAAGTCTCACTCTGTTTACTGATGCTGTGGGTCCTGTCTGGTTGTATCTTCCCACATGAAGGTGCTTTAGAGACACATTTTCCCTGCCTCGTGCCTTAGTCCTCTTTGTTGTTTTGTGGCTAGGTGACTTTTCACACTGGGCTTGAACACTGTCAGTGATGGTGAAATCCTTGCCACAGCTTTGGGAGTCTCTTGCAGTCTCCCAGCAGTAGAGGGAGTTAGAAATATCCAGAGGGGAAAAAAAAATCTCTCTTTTCAGACAGTATCTGCTTTATTGGTGGTAGCTGAACTTCATTTATACAGAGCTCCTTTAACCTGTCTGTCTTCTTCTTGGTATCTAAGCTGCCTTTTGTTTTTGTTTTTGTTTTTGTTTTTATGATATTAACTTCTTTTCACATTCAAGTTTCTTTAAAGTTGACTATAGTGCCTTCTGAACTCTTGCAGAGAGTTTGGATTTTGGAAGCTGCCAGGTACCCATCACAGCAGGGGTGCCAGTGACAAGGATGGTGTACAAATGAAACACTGAAGCTATCCAAATAAATTCCTCTAAGTGTAATTCATTTTACTGCAGCACAGGAAGAACAAATTTGTCTTACAACTTTAATAATTAGTACCATTATGAACCCTAGGAGAGAAATAAGAGCAAATACCTGTTGAATAAATGAATGTAAGAAAATGTGTGTCTGAGCAAGAATACTCTGTCTGGCTACTATGGGAAGCTAGCTAGATCTGAAAGACATTCTCAGACTATCCTCATGTTCAAGGCATTAAAGGAATAAGCCTCCAGCCCCTAACCTTAGGAGAATTCTGCAGTCAAGTGAGGAGTTTTTAAAACAGGAATCTCTAGGTTCCAGTCCTCTAGCTATTCTTTTATGCTTAGTCCAGGTAATGAGTTGAACATCCAAGTATTTTTTAAGGACCCAAAGAAATGCAACCAGAGCTATTACCAGAATTTTGGAGTGGTCCTCCTAGAGTTGCCGCATGTTGCTGGGAAAATTGGGGTCTTAGAGTTCTTAGTCTACTTAATAAAAGAATTTTAAAAAATGG (SEQ ID NO: 87) >NP_848874.3 T-cell immunoglobulin and mucin domain-containing protein 4 precursor [Mus musculus]MSKGLLLLWLVTELWWLYLTPAASEDTIIGFLGQPVTLPCHYLSWSQSRNSMCWGKGSCPNSKCNAELLRTDGTRIISRKSTKYTLLGKVQFGEVSLTISNTNRGDSGVYCCRIEVPGWFNDVKKNVRLELRRATTTKKPTTTTRPTTTPYVTTTTPELLPTTVMTTSVLPTTTPPQTLATTAFSTAVTTCPSTTPGSFSQETTKGSAFTTESETLPASNHSQRSMMTISTDIAVLRPTGSNPGILPSTSQLTTQKTTLTTSESLQKTTKSHQINSRQTILIIACCVGFVLMVLLFLAFLLRGKVTGANCLQRHKRPDNTEDSDSVLNDMSHGRDDEDGIFTL (SEQ ID NO: 88) Human>NM_001712.5 Homo sapiens CEA cell adhesion molecule CEACAM11 (CEACAM1), transcript variant 1, mRNAAGCACAGAGAGTGGAAAACAGCAGAGGTGACAGAGCAGCCGTGCTCGAAGCGTTCCTGGAGCCCAAGCTCTCCTCCACAGGTGAAGACAGGGCCAGCAGGAGACACCATGGGGCACCTCTCAGCCCCACTTCACAGAGTGCGTGTACCCTGGCAGGGGCTTCTGCTCACAGCCTCACTTCTAACCTTCTGGAACCCGCCCACCACTGCCCAGCTCACTACTGAATCCATGCCATTCAATGTTGCAGAGGGGAAGGAGGTTCTTCTCCTTGTCCACAATCTGCCCCAGCAACTTTTTGGCTACAGCTGGTACAAAGGGGAAAGAGTGGATGGCAACCGTCAAATTGTAGGATATGCAATAGGAACTCAACAAGCTACCCCAGGGCCCGCAAACAGCGGTCGAGAGACAATATACCCCAATGCATCCCTGCTGATCCAGAACGTCACCCAGAATGACACAGGATTCTACACCCTACAAGTCATAAAGTCAGATCTTGTGAATGAAGAAGCAACTGGACAGTTCCATGTATACCCGGAGCTGCCCAAGCCCTCCATCTCCAGCAACAACTCCAACCCTGTGGAGGACAAGGATGCTGTGGCCTTCACCTGTGAACCTGAGACTCAGGACACAACCTACCTGTGGTGGATAAACAATCAGAGCCTCCCGGTCAGTCCCAGGCTGCAGCTGTCCAATGGCAACAGGACCCTCACTCTACTCAGTGTCACAAGGAATGACACAGGACCCTATGAGTGTGAAATACAGAACCCAGTGAGTGCGAACCGCAGTGACCCAGTCACCTTGAATGTCACCTATGGCCCGGACACCCCCACCATTTCCCCTTCAGACACCTATTACCGTCCAGGGGCAAACCTCAGCCTCTCCTGCTATGCAGCCTCTAACCCACCTGCACAGTACTCCTGGCTTATCAATGGAACATTCCAGCAAAGCACACAAGAGCTCTTTATCCCTAACATCACTGTGAATAATAGTGGATCCTATACCTGCCACGCCAATAACTCAGTCACTGGCTGCAACAGGACCACAGTCAAGACGATCATAGTCACTGAGCTAAGTCCAGTAGTAGCAAAGCCCCAAATCAAAGCCAGCAAGACCACAGTCACAGGAGATAAGGACTCTGTGAACCTGACCTGCTCCACAAATGACACTGGAATCTCCATCCGTTGGTTCTTCAAAAACCAGAGTCTCCCGTCCTCGGAGAGGATGAAGCTGTCCCAGGGCAACACCACCCTCAGCATAAACCCTGTCAAGAGGGAGGATGCTGGGACGTATTGGTGTGAGGTCTTCAACCCAATCAGTAAGAACCAAAGCGACCCCATCATGCTGAACGTAAACTATAATGCTCTACCACAAGAAAATGGCCTCTCACCTGGGGCCATTGCTGGCATTGTGATTGGAGTAGTGGCCCTGGTTGCTCTGATAGCAGTAGCCCTGGCATGTTTTCTGCATTTCGGGAAGACCGGCAGGGCAAGCGACCAGCGTGATCTCACAGAGCACAAACCCTCAGTCTCCAACCACACTCAGGACCACTCCAATGACCCACCTAACAAGATGAATGAAGTTACTTATTCTACCCTGAACTTTGAAGCCCAGCAACCCACACAACCAACTTCAGCCTCCCCATCCCTAACAGCCACAGAAATAATTTATTCAGAAGTAAAAAAGCAGTAATGAAACCTGTCCTGCTCACTGCAGTGCTGATGTATTTCAAGTCTCTCACCCTCATCACTAGGAGATTCCTTTCCCCTGTAGGGGTAGAGGGGTGGGGACAGAAACAACTTTCTCCTACTCTTCCTTCCTAATAGGCATCTCCAGGCTGCCTGGTCACTGCCCCTCTCTCAGTGTCAATAGATGAAAGTACATTGGGAGTCTGTAGGAAACCCAACCTTCTTGTCATTGAAATTTGGCAAAGCTGACTTTGGGAAAGAGGGACCAGAACTTCCCCTCCCTTCCCCTTTTCCCAACCTGGACTTGTTTTAAACTTGCCTGTTCAGAGCACTCATTCCTTCCCACCCCCAGTCCTGTCCTATCACTCTAATTCGGATTTGCCATAGCCTTGAGGTTATGTCCTTTTCCATTAAGTACATGTGCCAGGAAACAAGAGAGAGAGAAAGTAAAGGCAGTAATGCCTTCTCCTATTTCTCCAAAGCCTTGTGTGAACTCACCAAACACAAGAAAATCAAATATATAACCAATAGTGAAATGCCACACCTTTGTCCACTGTCAGGGTTGTCTACCTGTAGGATCAGGGTCTAAGCACCTTGGTGCTTAGCTAGAATACCACCTAATCCTTCTGGCAAGCCTGTCTTCAGAGAACCCACTAGAAGCAACTAGGAAAATCACTTGCCAAAATCCAAGGCAATTCCTGATGGAAAATGCAAAAGCACATATATGTTTTAATATCTTTATGGGCTCTGTTCAAGGCAGTGCTGAGAGGGAGGGGTTATAGCTTCAGGAGGGAACCAGCTTCTGATAAACACAATCTGCTAGGAACTTGGGAAAGGAATCAGAGAGCTGCCCTTCAGCGATTATTTAAATTATTGTTAAAGAATACACAATTTGGGGTATTGGGATTTTTCTCCTTTTCTCTGAGACATTCCACCATTTTAATTTTTGTAACTGCTTATTTATGTGAAAAGGGTTATTTTTACTTAGCTTAGCTATGTCAGCCAATCCGATTGCCTTAGGTGAAAGAAACCACCGAAATCCCTCAGGTCCCTTGGTCAGGAGCCTCTCAAGATTTTTTTTGTCAGAGGCTCCAAATAGAAAATAAGAAAAGGTTTTCTTCATTCATGGCTAGAGCTAGATTTAACTCAGTTTCTAGGCACCTCAGACCAATCATCAACTACCATTCTATTCCATGTTTGCACCTGTGCATTTTCTGTTTGCCCCCATTCACTTTGTCAGGAAACCTTGGCCTCTGCTAAGGTGTATTTGGTCCTTGAGAAGTGGGAGCACCCTACAGGGACACTATCACTCATGCTGGTGGCATTGTTTACAGCTAGAAAGCTGCACTGGTGCTAATGCCCCTTGGGGAAATGGGGCTGTGAGGAGGAGGATTATAACTTAGGCCTAGCCTCTTTTAACAGCCTCTGAAATTTATCTTTTCTTCTATGGGGTCTATAAATGTATCTTATAATAAAAAGGAAGGACAGGAGGAAGACAGGCAAATGTACTTCTCACCCAGTCTTCTACACAGATGGAATCTCTTTGGGGCTAAGAGAAAGGTTTTATTCTATATTGCTTACCTGATCTCATGTTAGGCCTAAGAGGCTTTCTCCAGGAGGATTAGCTTGGAGTTCTCTATACTCAGGTACCTCTTTCAGGGTTTTCTAACCCTGACACGGACTGTGCATACTTTCCCTCATCCATGCTGTGCTGTGTTATTTAATTTTTCCTGGCTAAGATCATGTCTGAATTATGTATGAAAATTATTCTATGTTTTTATAATAAAAATAATATATCAGACATCGA (SEQID NO: 89) >NP_001703.2 carcinoembryonic antigen-related celladhesion molecule 1 isoform 1 precursor [Homo sapiens]MGHLSAPLHRVRVPWQGLLLTASLLTFWNPPTTAQLTTESMPFNVAEGKEVLLLVHNLPQQLFGYSWYKGERVDGNRQIVGYAIGTQQATPGPANSGRETIYPNASLLIQNVTQNDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPETQDTTYLWWINNQSLPVSPRLQLSNGNRTLTLLSVTRNDTGPYECEIQNPVSANRSDPVTLNVTYGPDTPTISPSDTYYRPGANLSLSCYAASNP PAQYSWLINGTFQQSTQELFIPNITVNNSGSYTCHANNSVTGCNRTTVKTIIVTELSPVVAKPQIKASKTTVTGDKDSVNLTCSTNDTGISIRWFFKNQSLPSSERMKLSQGNTTLSINPVKREDAGTYWCEVFNPISKNQSDPIMLNVNYNALPQENGLSPGAIAGIVIGVVALVALIAVALACFLHFGKTGRASDQRDLTEHKPSVSNHTQDHSNDPPNKMNEVTYSTLNFEAQQPTQPTSASPSLTATEIIYSEVKKQ (SEQ ID NO: 90) Mouse>NM_001039185.1 Mus musculus carcinoembryonic CEACAM1antigen-related cell adhesion molecule 1 (Ceacam1),transcript variant 1, mRNAAAAGCTCCTTTAAGAAAAGCAGGGCAGATATCAGGGCAGCCTGGCTTAGCAGTAGTGTTGGAGAAGAAGCTAGCAGGCAGGCAGCAGAGACATGGAGCTGGCCTCAGCACATCTCCACAAAGGGCAGGTTCCCTGGGGAGGACTACTGCTCACAGCCTCACTTTTAGCCTCCTGGAGCCCTGCCACCACTGCTGAAGTCACCATTGAGGCTGTGCCGCCCCAGGTTGCTGAAGACAACAATGTTCTTCTACTTGTTCACAATCTGCCCCTGGCGCTTGGAGCCTTTGCCTGGTACAAGGGAAACACTACGGCTATAGACAAAGAAATTGCACGATTTGTACCAAATAGTAATATGAATTTCACGGGGCAAGCATACAGCGGCAGAGAGATAATATACAGCAATGGATCCCTGCTCTTCCAAATGATCACCATGAAGGATATGGGAGTCTACACACTAGATATGACAGATGAAAACTATCGTCGTACTCAGGCGACTGTGCGATTTCATGTACACCCCATATTATTAAAGCCCAACATCACAAGCAACAACTCCAATCCCGTGGAGGGTGACGACTCCGTATCATTAACCTGTGACTCTTACACTGACCCTGATAATATAAACTACCTGTGGAGCAGAAATGGTGAAAGCCTTTCAGAAGGTGACAGGCTGAAGCTGTCTGAGGGCAACAGGACTCTCACTTTACTCAATGTCACGAGGAATGACACAGGACCCTATGTGTGTGAAACCCGGAATCCAGTGAGTGTCAACCGAAGTGACCCATTCAGCCTGAACATTATCTATGGTCCGGACACCCCGATTATATCCCCCTCAGATATTTATTTGCATCCAGGGTCAAACCTCAACCTCTCCTGCCATGCAGCCTCTAACCCACCTGCACAGTACTTTTGGCTTATCAATGAGAAGCCCCATGCATCCTCCCAAGAGCTCTTTATCCCCAACATCACTACTAATAATAGCGGAACCTATACCTGCTTCGTCAATAACTCTGTCACTGGCCTCAGTAGGACCACAGTCAAGAACATTACAGTCCTTGAGCCAGTGACTCAGCCCTTCCTCCAAGTCACCAACACCACAGTCAAAGAACTAGACTCTGTGACCCTGACCTGCTTGTCGAATGACATTGGAGCCAACATCCAGTGGCTCTTCAATAGCCAGAGTCTTCAGCTCACAGAGAGAATGACACTCTCCCAGAACAACAGCATCCTCAGAATAGACCCTATTAAGAGGGAAGATGCCGGCGAGTATCAGTGTGAAATCTCGAATCCAGTCAGCGTCAGGAGGAGCAACTCAATCAAGCTGGACATAATATTTGACCCAACACAAGGAGGCCTCTCAGATGGCGCCATTGCTGGCATCGTGATTGGAGTTGTGGCTGGGGTGGCTCTAATAGCAGGGCTGGCATATTTCCTCTATTCCAGGAAGTCTGGCGGGGGAAGTGACCAGCGAGATCTCACAGAGCACAAACCCTCAGCCTCCAACCACAATCTGGCTCCTTCTGACAACTCTCCTAACAAGGTGGATGACGTCGCATACACTGTCCTGAACTTCAATTCCCAGCAACCCAACCGGCCAACTTCAGCCCCTTCTTCTCCAAGAGCCACAGAAACAGTTTATTCAGAAGTAAAAAAGAAGTGAGCATAATCTGTCCGTCTGTCCTGCTGGCTGCACCAGTGATGCATTCCCGGATTCTGTTCCTCACTGGAGGGTCTCAGCACACACACACACGTACACATGCGCGCGCGCACACACACACACACACACACACACACACACTTACACACACACTCATGCATTCACTCTATTGACTCCTTCAGTGTCTATAGAAGAAAAGGTGGATCCTGGAGCCTACAGAAAACTCAACCCTTCTAGGCTTTCAAATTTGGCTGAGAGTGAGGTATCAAAATTTCTCACCCTTTCACTTTCCTGACCCAGATTGTTGAAAATTGACCTATTCAGAGCACCTTCATTCCCCTCCCAACTCCAAGTCCTGCCCTATCAGAGTCTGACTTGAATTTCCATAAACCTTGGAGGTCACCTAAGTGCTTACGCCAAACAAAACAAAACAAAACAAAACAAAACAAAACAAAACAAAACAAAACAAACCAGAAGCAGGAAATGGCCAGTCCCATATCTTTAAAGGCTGATTGGAAGCCACCATACATGAGAAGATCAAACCTCCATGGGCAATCTACACACCCGACAACTGTCATGCTTACCCATCTGGGACATTCGAGTCTCTGAACCTTGTGCCCTCACGCCTGAGCCCTTCTCTGAGCCTTTCTCCAGAAAATCCACTCACAGCAACTAGAGAGGCTCTTTGTCAGCAACTCCAAGCAAACTGCTAGGCAGGATTCAGAAGAAAAGACAGCATCTCTAACATCCACCAGGAAGGTGCCCAGAAAAGCAGAGCTGGTGACTTTGGACTGACAGACATCTGGAGTGTGAAAAAGCAGCACAGAGCTAACCTTCGGAGAGTGTTGAAATTATTTGAAAAGAAGCCATATTTGGAGGTATTGGAGTTTTCCTCTTTCTGAGACAATCCACTATTTGAAAATTGTAGCTACTGAATTGCCTCTCAGTATGCGAGCTGATCACTTTGCCTTAGGGCCACTAGATTTCTGTCTCCCTTAGCCCCTCAAGCCCTTTTGATCATGAGTTCCAAACCAAAAATAAATAAATGAACAGTGAGGCAGTCCCTTGCAGTACCACTGTCATGGGTCAGGCTAAGCCTCCTGCTTTTCTGAATTAGTCAAGAAAAGCCTTGGTTTCCCTTTTTCCATCTCTTTATCTTGTCTTTCAGATACTGGCCAGAGCCTGGACACTCTTCCTCTGAGATCTCCAGCTTCTCTGCCTTCTTGTGTTTCTTTTAAACTCTAACAAAAACTGTTCTCACCTTCAAAAAATAAAATAATAACAAGCTTTCCACATCCCCACCAAAGAGGGACCCAGCTAGGTTTCTGGAAACCCAGCACCAGCCTCCAGCTGCCCTTCTGCAGTGTTTCTGCCTCTGTTTCCCTTTCGTTTTGACTTTTTTCCTTCTTTTGAGACAGAGTTCCAGCATGGAGCCTGTGCAGGTTTCAATCCCACAGTAACACCTTCTGCAGCACCCCACCTGCTCAGACTGCAGCCCTGGCCACCAGGCCTGGCTACCTGGACATTCTGTCTGCCCTGCACTCTCAGGAAACCTTGGCCTCTGCTACTGTCTGTTTGGCTCATTCAAAGTGTGTCCTTAAAGGAATGCAGTCACCCATGCCAGAGGCAGTGTTTACAGCCTGGAATGCTCTGCACTTCCAGTGGACCAGTGCTCCACCGGAAGTGGGCTGTTAGCAGGGTCCTCTCACCTGGCCCTGGCCTTTCTGTAGCCTTGAATCCTGCCTTCCCCACCAGGGCACCAGGGATGAGTGCAGCAGCAGGAGGAGAGGCAAACAGTCACCTCAGGAACCTTCTGAGCTAAGGCACACCCTCTGTGCCTGTCAAGCAAAGGTTGTATTGGATATCAAGTGTTTGGTCTCACGCCAAGCCAACAGGCTTTGGAGAGAATTAATTAGTTCTCCTACTCAGGGATTTCTTTCAGTCCTAACACAGCCTGTGTATATTTTGCTTCACCCACGCAATGCTGGATTATTTAATTTTGCCCGGCTTAAGACAAATCTGAGTTACTTGTAAATTTGCTCTATGTTCATAATAAAAATGTATTATATATCACTGATAGCA (SEQ ID NO: 91) >NP_001034274.1 carcinoembryonic antigen-related celladhesion molecule 1 isoform 1 precursor [Mus musculus]MELASAHLHKGQVPWGGLLLTASLLASWSPATTAEVTIEAVPPQVAEDNNVLLLVHNLPLALGAFAWYKGNTTAIDKEIARFVPNSNMNFTGQAYSGREIIYSNGSLLFQMITMKDMGVYTLDMTDENYRRTQATVRFHVHPILLKPNITSNNSNPVEGDDSVSLTCDSYTDPDNINYLWSRNGESLSEGDRLKLSEGNRTLTLLNVTRNDTGPYVCETRNPVSVNRSDPFSLNIIYGPDTPIISPSDIYLHPGSNLNLSCHAASNPPAQYFWLINEKPHASSQELFIPNITTNNSGTYTCFVNNSVTGLSRTTVKNITVLEPVTQPFLQVTNTTVKELDSVTLTCLSNDIGANIQWLENSQSLQLTERMTLSQNNSILRIDPIKREDAGEYQCEISNPVSVRRSNSIKLDIIFDPTQGGLSDGAIAGIVIGVVAGVALIAGLAYFLYSRKSGGGSDQRDLTEHKPSASNHNLAPSDNSPNKVDDVAYTVLNFNSQQPNRPTSAPSSPRATETVYSEVKKK (SEQ ID NO: 92) Human>NM_007048.6 Homo sapiens butyrophilin subfamily 3 BTN3A1member A1 (BTN3A1), transcript variant 1, mRNAATTCCTCACGATGACCCGACAGTCTCTGCTTTCTTTTTCCTTTCTTCCAGAAGGAGATTTAACCATAGTAGAAAGAATGGAGAACTATTAACTGCCTTTCTTCTGTGGGCTGTGATTTTCAGAGGGGAATGCTAAGAGGTGATTTTCAATGTTGGGACTCAAAGGTGAAGACACTGAAGGACAGAATTTTTGGCAGAGGAAAGATCTTCTTCGGTCACCATACTTGAGTTAGCTCTAGGGAAGTGGAGGTTTCCATTTGGAATTCTATAGCTTCTTCCAGGTCATAGTGTCTGCCCCCCACCTTCCAGTATCTCCTGATATGCAGCATGAATGAAAATGGCAAGTTTCCTGGCCTTCCTTCTGCTCAACTTTCGTGTCTGCCTCCTTTTGCTTCAGCTGCTCATGCCTCACTCAGCTCAGTTTTCTGTGCTTGGACCCTCTGGGCCCATCCTGGCCATGGTGGGTGAAGACGCTGATCTGCCCTGTCACCTGTTCCCGACCATGAGTGCAGAGACCATGGAGCTGAAGTGGGTGAGTTCCAGCCTAAGGCAGGTGGTGAACGTGTATGCAGATGGAAAGGAAGTGGAAGACAGGCAGAGTGCACCGTATCGAGGGAGAACTTCGATTCTGCGGGATGGCATCACTGCAGGGAAGGCTGCTCTCCGAATACACAACGTCACAGCCTCTGACAGTGGAAAGTACTTGTGTTATTTCCAAGATGGTGACTTCTATGAAAAAGCCCTGGTGGAGCTGAAGGTTGCAGCACTGGGTTCTGATCTTCACGTTGATGTGAAGGGTTACAAGGATGGAGGGATCCATCTGGAGTGCAGGTCCACTGGCTGGTACCCCCAACCCCAAATACAGTGGAGCAACAACAAGGGAGAGAACATCCCGACTGTGGAAGCACCTGTGGTTGCAGACGGAGTGGGCCTGTATGCAGTAGCAGCATCTGTGATCATGAGAGGCAGCTCTGGGGAGGGTGTATCCTGTACCATCAGAAGTTCCCTCCTCGGCCTGGAAAAGACAGCCAGCATTTCCATCGCAGACCCCTTCTTCAGGAGCGCCCAGAGGTGGATCGCCGCCCTGGCAGGGACCCTGCCTGTCTTGCTGCTGCTTCTTGGGGGAGCCGGTTACTTCCTGTGGCAACAGCAGGAGGAAAAAAAGACTCAGTTCAGAAAGAAAAAGAGAGAGCAAGAGTTGAGAGAAATGGCATGGAGCACAATGAAGCAAGAACAAAGCACAAGAGTGAAGCTCCTGGAGGAACTCAGATGGAGAAGTATCCAGTATGCATCTCGGGGAGAGAGACATTCAGCCTATAATGAATGGAAAAAGGCCCTCTTCAAGCCTGCGGATGTGATTCTGGATCCAAAAACAGCAAACCCCATCCTCCTTGTTTCTGAGGACCAGAGGAGTGTGCAGCGTGCCAAGGAGCCCCAGGATCTGCCAGACAACCCTGAGAGATTTAATTGGCATTATTGTGTTCTCGGCTGTGAGAGCTTCATATCAGGGAGACATTACTGGGAGGTGGAGGTAGGGGACAGGAAAGAGTGGCATATAGGGGTGTGCAGTAAGAATGTGCAGAGAAAAGGCTGGGTCAAAATGACACCTGAGAATGGATTCTGGACTATGGGGCTGACTGATGGGAATAAGTATCGGACTCTAACTGAGCCCAGAACCAACCTGAAACTTCCTAAGCCCCCTAAGAAAGTGGGGGTCTTCCTGGACTATGAGACTGGAGATATCTCATTCTACAATGCTGTGGATGGATCGCATATTCATACTTTCCTGGACGTCTCCTTCTCTGAGGCTCTATATCCTGTTTTCAGAATTTTGACCTTGGAGCCCACGGCCCTGACTATTTGTCCAGCGTGAAAAGAAGAAGAGAGTTCCTCCAATTCTGACCGAGTGCTGATCATTCCCTAGAGACACCAGTAACCCCGGGCTTAGCTAACGAAAGTGGGGAGCCTCAGGCTGAAGTAACTTTTCTCTGCTTCTCCCTGCCCAGCTCAGAGCTGAGGGCCTCCCCCTCCACAGCAACCAATCACAACCATAAAGCTACAAGCACGCACTGAAGCACTTTACTGATACTCATTCAATTATTCATATGACAGTTGTTTGAGTTTGGTACCATCTTATTTTCCCCTTATACAGATAAGGAAACTGGGGTGCAGAAAAGTGAATTGACTACAAAGTAGACATGACTAGTTAACAACACAGCTGGGATCTAAACAGCAATAACTAACATTAATGGAGAACTTAAAATGCTCTGAGTGCTGTGTTATGAGCTTTGGTGGATGTCACTCCTTTAATCCTCGCAACACCCTGTCGGGTAGTCTCATTTAGCAAGTATGGAAGTTGAGGCAGGGCAACATTAAGCAACTTACATAACTCATGCAGTAATTTCTGCAGTTGGGAGATGTTCAGCTTCAGTCCCCGGCCCTATGGCCGTTCTTTTCCACCCTGTTTCTTCCCCCATAGGAAGAACCCACCTGTAGCCCTGAGGTTCTTTTCCCAGGATGGCTCCAGGATAAGGATCACTGTAGGTGGTTGTGGAGTTGACACCCCTGTTGACTCCTTCCCAGCTGATTGTCAGAGCCTTAGACCCAGCACGCCTTGGATTAGCTCTGCAGAGTGTCTTGGTTGAGAGAATAACCTCACCGTACCCACATGACACGTGATTTGGAAAGAGACTAGAGGCCACACTTGATAAATCATGGGGAACAGATGTGTTCCACCCAACAAATGTGATAAGTGATCATGCAGCCAGAGCCAGCCTTCCTTCAATCAAGGTTTCCAGGCAGAGCAAATACCCTAGAGATTCTCTGTGATATAGGAAATTTGGATGAAGGGAGCTAGAAGAAATACAGGGATTTTTTTTTTTTTTTAAGATGGAGTCTTACTCTGTTGCTAGGCTGGAGTGCAGTGGTGCGATCTCAGCTCCCTGCAACCTCCACCTCCTGGGTTCAAACAATTCTCCTGCCTCAGCCTCCCGAGTACTGGGAATATAGGTGCACGCCACCACACCCAACAAATTTTTGTACTTTTAGTACAGATGAGGGTTCACTATGTTGGCCAGGATGGTCTCGATCTCTTGACCTCATGATCCACCCACCTCGGTCTCCCAAAGTGCTGGGATTACAGGCTTGAGCCACCGGGTGACCGGCTTACAGGGATATTTTTAATCCCGTTATGGACTCTGTCTCCAGGAGAGGGGTCTATCCACCCCTGCTCATTGGTGGATGTTAAACCAATATTCCTTTCAACTGCTGCCTGCTAGGGAAAAACTACTCCTCATTATCATCATTATTATTGCTCTCCACTGTATCCCCTCTACCTGGCATGTGCTTGTCAAGTTCTAGTTGTTCAATAAATTTGTTAATAATGCTGA(SEQ ID NO: 93) >NP_008979.3 butyrophilin subfamily 3 member Alisoform a precursor [Homo sapiens]MKMASFLAFLLLNFRVCLLLLQLLMPHSAQFSVLGPSGPILAMVGEDADLPCHLFPTMSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIHNVTASDSGKYLCYFQDGDFYEKALVELKVAALGSDLHVDVKGYKDGGIHLECRSTGWYPQPQIQWSNNKGENIPTVEAPVVADGVGLYAVAASVIMRGSSGEGVSCTIRSSLLGLEKTASISIADPFFRSAQRWIAALAGTLPVLLLLLGGAGYFLWQQQEEKKTQFRKKKREQELREMAWSTMKQEQSTRVKLLEELRWRSIQYASRGERHSAYNEWKKALFKPADVILDPKTANPILLVSEDQRSVQRAKEPQDLPDNPERFNWHYCVLGCESFISGRHYWEVEVGDRKEWHIGVCSKNVQRKGWVKMTPENGFWTMGLTDGNKYRTLTEPRTNLKLPKPPKKVGVFLDYETGDISFYNAVDGSHIHTFLDVSFSEALYPVFRILTLEPTALTICPA (SEQ ID NO: 94) Human>NM_007047.5 Homo sapiens butyrophilin subfamily 3 BTN3A2member A2 (BTN3A2), transcript variant 1, mRNAGACTCTTACTGTTTCTCATGGTGAGAAGACAATATTTGCTTTCTCTTTTTCCTTTCTTCCGGATGAGAGGCTAAGCCATAATAGAAAGAATGGAGAATTATTGATTGACCGTCTTTATTCTGTGGGCTCTGATTCTCCAATGGGAATACCAAGGGATGGTTTTCCATACTGGAACCCAAAGGTAAAGACACTCAAGGACAGACATTTTTGGCAGAGCATAGATGAAAATGGCAAGTTCCCTGGCTTTCCTTCTGCTCAACTTTCATGTCTCCCTCCTCTTGGTCCAGCTGCTCACTCCTTGCTCAGCTCAGTTTTCTGTGCTTGGACCCTCTGGGCCCATCCTGGCCATGGTGGGTGAAGACGCTGATCTGCCCTGTCACCTGTTCCCGACCATGAGTGCAGAGACCATGGAGCTGAAGTGGGTAAGTTCCAGCCTAAGGCAGGTGGTGAACGTGTATGCAGATGGAAAGGAAGTGGAAGACAGGCAGAGTGCACCGTATCGAGGGAGAACTTCGATTCTGCGGGATGGCATCACTGCAGGGAAGGCTGCTCTCCGAATACACAACGTCACAGCCTCTGACAGTGGAAAGTACTTGTGTTATTTCCAAGATGGTGACTTCTATGAAAAAGCCCTGGTGGAGCTGAAGGTTGCAGCACTGGGTTCTAATCTTCACGTCGAAGTGAAGGGTTATGAGGATGGAGGGATCCATCTGGAGTGCAGGTCCACCGGCTGGTACCCCCAACCCCAAATACAGTGGAGCAACGCCAAGGGAGAGAACATCCCAGCTGTGGAAGCACCTGTGGTTGCAGATGGAGTGGGCCTATATGAAGTAGCAGCATCTGTGATCATGAGAGGCGGCTCCGGGGAGGGTGTATCCTGCATCATCAGAAATTCCCTCCTCGGCCTGGAAAAGACAGCCAGCATTTCCATCGCAGACCCCTTCTTCAGGAGCGCCCAGCCCTGGATCGCAGCCCTGGCAGGGACCCTGCCTATCTTGCTGCTGCTTCTCGCCGGAGCCAGTTACTTCTTGTGGAGACAACAGAAGGAAATAACTGCTCTGTCCAGTGAGATAGAAAGTGAGCAAGAGATGAAAGAAATGGGATATGCTGCAACAGAGCGGGAAATAAGCCTAAGAGAGAGCCTCCAGGAGGAACTCAAGAGGAAAAAAATCCAGTACTTGACTCGTGGAGAGGAGTCTTCGTCCGATACCAATAAGTCAGCCTGATGCTCTAATGGAAAAATGGCCCTCTTCAAGCCTGGTGAGGAAATGCTTCAGATGAGGCTCCACCTTGTTAAATAAATTGGATGTATGGAAAAATAGACTGCAGAAAAGGGGAACTCATTTAGCTCACGAGTGGTCGAGTGAAGATTGAAAATTAACCTCTGAGGGCCAGCACAGCAGCTCATGCCTGTAATCCTAGCACTTTGGAAGGCTGAGGAGGGCGGATCACAAGGTCAGGAGATCAAGACCATCCTGGCTAACACGGTGAAACCCCGTCTCTACTAAAAATACAAAAAATAAAAAATTAGCCGGGCATGGTGACGGGCACCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAATGGCATGAACCCGGAAGGCAGAGCTTGCAGTGAGCCGAGATCACGCCACTGCACTCCAGCCTGGGAGACAGAGCGAGACTCTGTCTCAAGAAAAAAAAAAAAAAAAAAAAAGAAAAGAAAATTAACCTCTGAGTATAAAGCATCAGTGGGCAGAATCAATGTGGGGAGGGAAACAACAAAAATGTAGAAAGAGGATCCTTGTTGCTTCTTGGGGCCGCATCAGGGTATTGGGTTAGGCAGATACTGACCTTACTTTCATTTCCCCTCTGGTCACTAGACCCCTGGGGCTTTCACCAATGACATTGATGAGAGAATCACATTCAGGGCAGGCTAGGGACACGGGGTTCTGGAAGGACCTCCTCAGCATGGCCCAAGCCTTGCATGCTGTGGCTCTTAAATCCAGGAAAAATGGCTGACCCCATGGACACCTCCTCAAACTCTCTGCAGCAGATGTAATTCTGTATCCAGACATGGCAAATGCCATCCTCCTTGTTTCTGAGGACCAGAGGAGTGTACAGCGTGCTGAGGAGCCCCATGACCTACCAGACAACCCTGAGAGATTTGAATGGCGTTACTGTGTGCTTGGCTGTGAAAGCTTCATGTCAGAGAGACACTACTGGGAGGTGGAAGTGGGGGACAGAAAAGAGTGGCATATTGGGGTATGTAGTAAGAACGTGGAGAGGAAAAAAGTTTGGGTCAAAATGACACCGGAGAACGGATACTGGACTATGGGCCTGACTGATGGGAATAAGTATCGGGCTCTCACTGAGCCCAGAACCAACCTGAAACTTCCTGAGCCTCCTAGGAAAGTGGGGGTCATCCTGGACTATGAGACTGGACATATCTCGTTCTACAATGCCACGGATGGATCTCATATCTACACATTTCTGCACGCCTCTTCCTCTGAGCCTCTGTATCCTGTATTCAGAATTTTGACCTTGGAGCCCACTGCCCTGACCGTTTGCCCAATACCAAAAGTAGAGAGTTCCCCCGATCCCGACCTAGTGCCTGATCATTCCCTGGAGATACCACTGACCCCAGGCTTAGCTAATGAAAGTGGGGAGCCTCAGGCTGAAGTAACATCTCTGCTTCTCCCTGCCCAGCCTGGAGCTAAGGGTCTCACCCTCCACAACAGCCAGTCAGAACCATAAAGCTACAGGCACACACTGAAGCACTTTACTGATATTCATTCAATTATTCCATAGGACAGTTGTTTGAGTTTGGTGCCACCTTATTGGCCCCTTTATACAGATAAGGAAACTGGGGTGTAGAAAAGTGTATTGACTTTACAAAGCAGACAGGAATAGTGAACAACAGAGCTGGGATCTGAACAACAATGACTAACATTAATGGAGAATTTAAAACGTTCTGAGTGCTGTGTTATGAGCTTTGGTGGGTGTCACTCCTTTAATCCTCACAACACCCTGTCAGGTAGTCTCATTTGGCAAGTATGGAAGCAGAGGCAGGGCAACATTAAGTAGCTTACATAACTCACACGGTAATTTGTGCAGTTGGGAGATGTTCAGCTTCAGTCCCTGGCCAATTGCCCGTTCTTTTCCAGCCTGATTTTTCCTGCATGGGAAGAGCCCACATGTAGCCCTGAGGTTCCCTTCCCAGGACAGCTCCAGGATCGAGATCACTGTGAGTGGTTGTGGAGTTAAGACCCCTATGGACTCCTTCCCAGCTGATTATCAGAGCCTTAGACCCAGCACTCCTTGGATTGGCTCTGCAGAGTGTCTTGGTTGAGAGAATAACGTTGCAGTTCCCACAGGGCATGTGACTTTGAAAGAGACTAGAGGCCACACTCAGTTAATAATGGGGCACAGATGTGTTCCCACCCAACAAATGTGATAAGTGATCGTGCAGCCAGAGCCAGCCTTCCTTCAGTCAAGGTTTCCAGGCAGAGCAAATACCCTAGAGATTCTCTGTAATATTGGTAATTTGGATGAAGGAAGCTAGAAGAATTACAGGGATGTTTTTAATCCCACTATGGACTCAGTCTCCTGGAAAAGGATCTGTCCACTCCTGGTCATTGGTGGATGTTAAACCCATATTCCTTTCAACTGCTGCCTGCTAGGGAAAACTGCTCCTCATTATCATCACTATTATTGCTCACCACTGTATCCCCTCTACTGGGCAAGTGCTTGTCAAGTTCTAGTTGTTCAATAAATTTGTTAATAATGCTGA (SEQ ID NO: 95) >NP_008978.2 butyrophilin subfamily 3 member A2isoform a precursor [Homo sapiens]MKMASSLAFLLLNFHVSLLLVQLLTPCSAQFSVLGPSGPILAMVGEDADLPCHLFPTMSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIHNVTASDSGKYLCYFQDGDFYEKALVELKVAALGSNLHVEVKGYEDGGIHLECRSTGWYPQPQIQWSNAKGENIPAVEAPVVADGVGLYEVAASVIMRGGSGEGVSCIIRNSLLGLEKTASISIADPFFRSAQPWIAALAGTLPILLLLLAGASYFLWRQQKEITALSSEIESEQEMKEMGYAATEREISLRESLQEELKRKKIQYLTRGEESSSDTNKSA (SEQ ID NO: 96) Human>NM_007049.5 Homo sapiens butyrophilin subfamily 2 BTN2A1member A1 (BTN2A1), transcript variant 1, mRNAAGATTTCGTTTCCTGCATCTCCAAACATGGCGACCTAGGAGAAGGGGAAGAACAATTTTTTCTCCTCTTTTGGGAAGGTTTGTGTCTAGTAGTGCCTGTGCCCCTGGGCAGATTGGAGAGAAGAGGGACGACTGGAGAATCGTCGAGAACCAGCGGAGAAAAGAAAAAGCAACGTTTAATTCTAGAAGGCCTCCTGTCCCTGCCTGCTCTGGGTGCTCATGGAATCAGCTGCTGCCCTGCACTTCTCCCGGCCAGCCTCCCTCCTCCTCCTCCTCCTCAGCCTGTGTGCACTGGTCTCAGCCCAGTTTATTGTCGTGGGGCCCACTGATCCCATCTTGGCCACGGTTGGAGAAAACACTACGTTACGCTGCCATCTGTCACCCGAGAAAAATGCTGAGGACATGGAGGTGCGGTGGTTCCGGTCTCAGTTCTCCCCCGCAGTGTTTGTGTATAAAGGTGGCAGAGAGAGAACAGAGGAGCAGATGGAGGAGTACCGAGGAAGAACCACCTTTGTGAGCAAAGACATCAGCAGGGGCAGCGTGGCCCTGGTCATACACAACATCACAGCCCAGGAAAACGGCACCTACCGCTGTTACTTCCAAGAAGGCAGGTCCTACGATGAGGCCATCCTGCACCTCGTAGTGGCAGGACTAGGCTCTAAGCCCCTCATTTCAATGAGGGGCCATGAAGACGGGGGCATCCGGCTGGAGTGCATATCTAGAGGGTGGTACCCAAAGCCCCTCACAGTGTGGAGGGACCCCTACGGTGGGGTTGCGCCTGCCCTGAAAGAGGTCTCCATGCCTGATGCAGACGGCCTCTTCATGGTCACCACGGCTGTGATCATCAGAGACAAGTCTGTGAGGAACATGTCCTGCTCTATCAACAACACCCTGCTCGGCCAGAAGAAAGAAAGTGTCATTTTTATTCCAGAATCCTTTATGCCCAGTGTGTCTCCCTGTGCAGTGGCCCTGCCTATCATTGTGGTTATTCTGATGATACCCATTGCCGTATGCATCTATTGGATCAACAAACTCCAAAAGGAAAAAAAGATTCTGTCAGGGGAAAAGGAGTTTGAACGGGAAACAAGAGAAATTGCTCTAAAGGAACTGGAGAAAGAACGTGTGCAAAAAGAGGAAGAACTTCAAGTAAAAGAGAAACTTCAAGAAGAATTGCGATGGAGAAGAACATTCTTACATGCTGTTGATGTGGTCCTGGATCCAGACACCGCTCATCCCGATCTCTTCCTGTCAGAGGACCGGAGAAGTGTGAGAAGGTGCCCCTTCAGGCACCTAGGGGAGAGCGTGCCTGACAACCCAGAGAGATTCGACAGTCAGCCTTGTGTCCTAGGCCGGGAGAGCTTCGCTTCAGGGAAACATTACTGGGAGGTGGAGGTGGAAAACGTGATTGAGTGGACTGTGGGGGTCTGTAGAGACAGTGTTGAGAGGAAAGGGGAGGTCCTGCTGATTCCTCAGAATGGCTTCTGGACCTTGGAGATGCATAAAGGGCAATACCGGGCCGTGTCCTCCCCTGATAGGATTCTCCCTTTGAAGGAGTCCCTTTGCCGGGTGGGCGTCTTCCTGGACTATGAAGCTGGAGATGTCTCCTTCTACAACATGAGGGACAGATCGCACATCTACACATGTCCCCGTTCAGCCTTTTCCGTGCCTGTGAGGCCCTTCTTCAGGTTGGGGTGTGAGGACAGCCCCATCTTCATCTGCCCTGCACTCACAGGAGCCAATGGGGTCACGGTGCCTGAAGAGGGCCTGACACTTCACAGAGTGGGGACCCACCAGAGCCTATAGAATCAATTCCTTGGTCTCACAGCCATGTAGACAAGCCCTGGTCATCTCAGCAGCCACCGCACAACACCCCTGGTGGAAGACACGCCCTCCTCCCCTCTGGTCACACAAGAGAACATCTTCCAGCTGCCTCTTTCACACCCACTACAGACCTCAGCCCCAGTTTTCTCCTCCTCACTAGGCTGTGTTTTTAGTAGTTCCTTTGCTTGTAACTATGGGATGGGATCCAGGCATAGGGAACTAGTTGTTACACAGCTCCCAGCCAAGAAGAAAGTGTGAGAAGTTGATGGGCAGCAAACCTGCTGTTTAACATCAGGGTGACCACATTAAGCCCAGTATTCCAGTTGGCACCAGAAGATATGGACTTGGAATGAGGCCTACAGGGTTCACCAGGATGTAAGAGGAGAGAGGAATCCACAGGACCACCAGAGAGGAGAGGGAACCAGATATGCAGATCAGAGATAGAGGAAGTGGAACCAGAGAGCTGGGAGGGACCAAGGTTGTAAGGGTGGCTAAGTCCCACCATAACAGCTAAGGGGACCTGGGAGATGATGGCTCATTTCCACCCAGCCCCAGGATTTCCAGAGCGCACATCCACAGGCCTGGACCTGGGATGAAGATGAATGAAGAACATGGATGCACGTGGATGTAGTTTGGCTCAGGTGTCCCTGCAGTTGGCAAGGAGTCAGTACTCAGTCCCTGAGTGTGGCTGAAATTTGAGGTCCTGGCTGAGCCAAGGAGTAATGGACCAGATCTACCTCAGTATTCAAGTTCAGTGGGGACACCAGTGGCTTCAAACTTCCTGGTTTCATGATATCTTGAGACGCCTTACAAATGATGGAGGATTCCAAAGAGTTTTTGTTTATTTGGGTTAATATTTGTTGGTATTTATGGCATTTGAGATTGAAACTAAGAAATGTTTTAATTTATTACCTTTACAACATTTATTTACATTACATACATACATTTACAACATTTATTAATTTATATTAAAATAGCATGAATAAGCCAATTATAGGTTAATATAAGTAGAATGTTTGTGAAAAATAAGTATGGTATCCAAAGCAAAATAAATTTTATTGTGAAGTGTG (SEQ ID NO: 97) >NP_008980.1 butyrophilin subfamily 2 member A1isoform 1 precursor [Homo sapiens]MESAAALHFSRPASLLLLLLSLCALVSAQFIVVGPTDPILATVGENTTLRCHLSPEKNAEDMEVRWFRSQFSPAVFVYKGGRERTEEQMEEYRGRTTFVSKDISRGSVALVIHNITAQENGTYRCYFQEGRSYDEAILHLVVAGLGSKPLISMRGHEDGGIRLECISRGWYPKPLTVWRDPYGGVAPALKEVSMPDADGLFMVTTAVIIRDKSVRNMSCSINNTLLGQKKESVIFIPESFMPSVSPCAVALPIIVVILMIPIAVCIYWINKLQKEKKILSGEKEFERETREIALKELEKERVQKEEELQVKEKLQEELRWRRTFLHAVDVVLDPDTAHPDLFLSEDRRSVRRCPFRHLGESVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVERKGEVLLIPQNGFWTLEMHKGQYRAVSSPDRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFSVPVRPFFRLGCEDSPIFICPALTGANGVTVPEEGLTLHRVGTHQSL (SEQ ID NO: 98) Human>NM_001040462.3 Homo sapiens butyrophilin like 8 BTNL8(BTNL8), transcript variant 2, mRNAAGAACAGCGCAGTTTGCCCTCCGCTCACGCAGAGCCTCTCCGTGGCTTCCGCACCTTGAGCATTAGGCCAGTTCTCCTCTTCTCTCTAATCCATCCGTCACCTCTCCTGTCATCCGTTTCCATGCCGTGAGGTCCATTCACAGAACACATCCATGGCTCTCATGCTCAGTTTGGTTCTGAGTCTCCTCAAGCTGGGATCAGGGCAGTGGCAGGTGTTTGGGCCAGACAAGCCTGTCCAGGCCTTGGTGGGGGAGGACGCAGCATTCTCCTGTTTCCTGTCTCCTAAGACCAATGCAGAGGCCATGGAAGTGCGGTTCTTCAGGGGCCAGTTCTCTAGCGTGGTCCACCTCTACAGGGACGGGAAGGACCAGCCATTTATGCAGATGCCACAGTATCAAGGCAGGACAAAACTGGTGAAGGATTCTATTGCGGAGGGGCGCATCTCTCTGAGGCTGGAAAACATTACTGTGTTGGATGCTGGCCTCTATGGGTGCAGGATTAGTTCCCAGTCTTACTACCAGAAGGCCATCTGGGAGCTACAGGTGTCAGCACTGGGCTCAGTTCCTCTCATTTCCATCACGGGATATGTTGATAGAGACATCCAGCTACTCTGTCAGTCCTCGGGCTGGTTCCCCCGGCCCACAGCGAAGTGGAAAGGTCCACAAGGACAGGATTTGTCCACAGACTCCAGGACAAACAGAGACATGCATGGCCTGTTTGATGTGGAGATCTCTCTGACCGTCCAAGAGAACGCCGGGAGCATATCCTGTTCCATGCGGCATGCTCATCTGAGCCGAGAGGTGGAATCCAGGGTACAGATAGGAGATACCTTTTTCGAGCCTATATCGTGGCACCTGGCTACCAAAGTACTGGGAATACTCTGCTGTGGCCTATTTTTTGGCATTGTTGGACTGAAGATTTTCTTCTCCAAATTCCAGTGGAAAATCCAGGCGGAACTGGACTGGAGAAGAAAGCACGGACAGGCAGAATTGAGAGACGCCCGGAAACACGCAGTGGAGGTGACTCTGGATCCAGAGACGGCTCACCCGAAGCTCTGCGTTTCTGATCTGAAAACTGTAACCCATAGAAAAGCTCCCCAGGAGGTGCCTCACTCTGAGAAGAGATTTACAAGGAAGAGTGTGGTGGCTTCTCAGAGTTTCCAAGCAGGGAAACATTACTGGGAGGTGGACGGAGGACACAATAAAAGGTGGCGCGTGGGAGTGTGCCGGGATGATGTGGACAGGAGGAAGGAGTACGTGACTTTGTCTCCCGATCATGGGTACTGGGTCCTCAGACTGAATGGAGAACATTTGTATTTCACATTAAATCCCCGTTTTATCAGCGTCTTCCCCAGGACCCCACCTACAAAAATAGGGGTCTTCCTGGACTATGAGTGTGGGACCATCTCCTTCTTCAACATAAATGACCAGTCCCTTATTTATACCCTGACATGTCGGTTTGAAGGCTTATTGAGGCCCTACATTGAGTATCCGTCCTATAATGAGCAAAATGGAACTCCCATAGTCATCTGCCCAGTCACCCAGGAATCAGAGAAAGAGGCCTCTTGGCAAAGGGCCTCTGCAATCCCAGAGACAAGCAACAGTGAGTCCTCCTCACAGGCAACCACGCCCTTCCTCCCCAGGGGTGAAATGTAGGATGAATCACATCCCACATTCTTCTTTAGGGATATTAAGGTCTCTCTCCCAGATCCAAAGTCCCGCAGCAGCCGGCCAAGGTGGCTTCCAGATGAAGGGGGACTGGCCTGTCCACATGGGAGTCAGGTGTCATGGCTGCCCTGAGCTGGGAGGGAAGAAGGCTGACATTACATTTAGTTTGCTCTCACTCCATCTGGCTAAGTGATCTTGAAATACCACCTCTCAGGTGAAGAACCGTCAGGAATTCCCATCTCACAGGCTGTGGTGTAGATTAAGTAGACAAGGAATGTGAATAATGCTTAGATCTTATTGATGACAGAGTGTATCCTAATGGTTTGTTCATTATATTACACTTTCAGTAA (SEQ ID NO: 99) >NP_001035552.1 butyrophilin-like protein 8 isoform 2precursor [Homo sapiens]MALMLSLVLSLLKLGSGQWQVFGPDKPVQALVGEDAAFSCFLSPKTNAEAMEVRFFRGQFSSVVHLYRDGKDQPFMQMPQYQGRTKLVKDSIAEGRISLRLENITVLDAGLYGCRISSQSYYQKAIWELQVSALGSVPLISITGYVDRDIQLLCQSSGWFPRPTAKWKGPQGQDLSTDSRTNRDMHGLFDVEISLTVQENAGSISCSMRHAHLSREVESRVQIGDTFFEPISWHLATKVLGILCCGLFFGIVGLKIFFSKFQWKIQAELDWRRKHGQAELRDARKHAVEVTLDPETAHPKLCVSDLKTVTHRKAPQEVPHSEKRFTRKSVVASQSFQAGKHYWEVDGGHNKRWRVGVCRDDVDRRKEYVTLSPDHGYWVLRLNGEHLYFTLNPRFISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTLTCRFEGLLRPYIEYPSYNEQNGTPIVICPVTQESEKEASWQRASAIPETSNSESSSQATTPFLPRGEM (SEQ ID NO: 100) Human>NM_006995.5 Homo sapiens butyrophilin subfamily 2 BTN2A2member A2 (BTN2A2), transcript variant 1, mRNAGGGACTTTTTGGACACCCAGAGAACAGGTCCCAGATACCGAGTCCGCAACTCCAAACATCGCGATTAATAGGAGGCCTCTGGTCTCTGCCTGCCCTGGGTGCTCATGGAACCAGCTGCTGCTCTGCACTTCTCCCTGCCAGCCTCCCTCCTCCTCCTCCTGCTCCTCCTCCTTCTCAGCCTGTGTGCACTGGTCTCAGCCCAGTTTACTGTCGTGGGGCCAGCTAATCCCATCCTGGCCATGGTGGGAGAAAACACTACATTACGCTGCCATCTGTCACCCGAGAAAAATGCTGAGGACATGGAGGTGCGGTGGTTCCGGTCTCAGTTCTCCCCCGCAGTGTTTGTGTATAAGGGTGGGAGAGAGAGAACAGAGGAGCAGATGGAGGAGTACCGGGGAAGAATCACCTTTGTGAGCAAAGACATCAACAGGGGCAGCGTGGCCCTGGTCATACATAACGTCACAGCCCAGGAGAATGGGATCTACCGCTGTTACTTCCAAGAAGGCAGGTCCTACGATGAGGCCATCCTACGCCTCGTGGTGGCAGGCCTTGGGTCTAAGCCCCTCATTGAAATCAAGGCCCAAGAGGATGGGAGCATCTGGCTGGAGTGCATATCTGGAGGGTGGTACCCAGAGCCCCTCACAGTGTGGAGGGACCCCTACGGTGAGGTTGTGCCCGCCCTGAAGGAGGTTTCCATCGCTGATGCTGACGGCCTCTTCATGGTCACCACAGCTGTGATCATCAGAGACAAGTATGTGAGGAATGTGTCCTGCTCTGTCAACAACACCCTGCTCGGCCAGGAGAAGGAAACTGTCATTTTTATTCCAGAATCCTTTATGCCCAGCGCATCTCCCTGGATGGTGGCCCTAGCTGTCATCCTGACCGCATCTCCCTGGATGGTGTCCATGACTGTCATCCTGGCTGTTTTCATCATCTTCATGGCTGTCAGCATCTGTTGCATCAAGAAACTTCAAAGGGAAAAAAAGATTCTGTCAGGGGAAAAGAAAGTTGAACAAGAGGAAAAAGAAATTGCACAGCAACTTCAAGAAGAATTGCGATGGAGAAGAACATTCTTACATGCTGCTGATGTGGTCCTGGATCCAGACACCGCTCATCCCGAGCTCTTCCTGTCAGAGGACCGGAGAAGTGTGAGGCGGGGCCCCTACAGGCAGAGAGTGCCTGACAACCCAGAGAGATTCGACAGTCAGCCTTGTGTCCTGGGATGGGAGAGCTTCGCCTCAGGGAAACATTACTGGGAGGTGGAGGTGGAAAACGTGATGGTGTGGACTGTGGGGGTCTGCAGACACAGTGTTGAGAGGAAAGGGGAGGTCCTGCTGATTCCTCAGAATGGCTTCTGGACCCTGGAGATGTTTGGAAACCAATACCGGGCCCTGTCCTCCCCTGAGAGGATTCTCCCTTTGAAGGAGTCCCTTTGCCGGGTGGGCGTCTTCCTGGACTATGAAGCTGGAGATGTCTCCTTCTACAACATGAGGGACAGATCGCACATCTACACATGTCCCCGTTCAGCCTTTACTGTGCCTGTGAGGCCCTTCTTCAGGTTAGGGTCTGATGACAGCCCCATCTTCATCTGCCCTGCACTCACAGGAGCCAGTGGGGTCATGGTGCCTGAAGAGGGCCTGAAACTTCACAGAGTGGGGACCCACCAGAGCCTATAGAATCAATTCCTTGGACTCACAGCCATGCAGATAAGCCCTGGCCATCTCAGCAGCCACCGCACAACCCCCCTAATGAAAGACACGCCCTCCTCCCCTCTGGTCACGTAAGAGAACATCTTCCAGCTGCCTTTTTCACACCCACTCCAGCCCTCTGCCCCAGTTTTCTCCTCCTCACTAGTCTGTGGCTTTAGTAGTTCCTTTGCTTGTAATTATGGGATGGGATCCAGGCATAGGGAACTAGTTGTTTCATAGCTCCCAGTCAAAAAGAAAGTGAGAGAAGCTGTTGGGCAGCGAACCTACTGTTTAAAATCAGGATAACCACATTAAGCCCAATATGCCAGTTGGCACCAGATGCTGTGGACTTGGAATGAGGCCAACAGGGTTCACCAGGATGAGAGAGGAGAGAGGAATCCACAGGACCACCAGAAGGGAGAGGGAACCAGATATGCAGATCAGAGATAGAGGAAGTGGAACCAGAGAGCTGGGAGGGACCAAGGTTGTAAGGATGGCTAAGTCCCACCATAAGAGCTAAAGGGTCCTGGGAGATGATGGCTCATTTCCACCCAACCCCAGGATTTCCACAGCACACACCCACAGGCCTGGACCTGGGATGAAGATGAATGAAGAACATGGACTCATGTGGATGTGGTTTGGCTCAGATGTCCCTGCAATAAACAAGGGGTCAGTACTTAGTCCCTGAGTGTGGTTGAGGTTTGAGGTCCTGGTCGAGCAGGGCAGTACTGGACCAGGTCTACGTCAGCATTCAGGTTCAATGGGGACACCAGTGGCTTCAAACTTCCTGATCTAATTATGTTTTTAGACACTTAGAAGTTATTGAGGACTTTAAAGAGCTTTTGTTTATTTGGGTTAATATTTATGACATTTGACATTGAAACAAAAATTTAAAATGTTATCTTTTAATTTATGTTAAAATAGCATTAATAAATCAGTTATAGGTTAATGTAGATAGGATGTTTTGTGAAAAAGCAATCTATTGTGTCCAAATAAAAAAACAAAAAGTGTGACACTGGTTAACTTTTTCCAGATCTCATGTCTGGCTTAATAAGAGATATTTGTATTATCATATCTGCCTTTGTATTAAACCTATTGGTATATCATAGGTCATGTTAGCTCAAAAAAACTTTACTGCACACTACTGAGAGAATGAGATGAAAAACGATTAATGTTTCATTATTATTATTGTGAAAATATTATTAACACTGGGGACTCCTTAAGAGTACATCAGAGTTCTCTCTAGGAATCCCAAAACCACATTTTGAAACTAGAATAGTGGATCCTGGAAGTTAATCCATGTGCTGGTTAATTTTAGATGTCAACCTGACTGGATTAAGGAATACCTAGACAGCTGGTACAACATTATTTCTGGGTGTGTCTGTGAGTGTGTTTCCAGAAGAGATTGGCAAGTGAGTCAGTGGGAAATTCTCTCCTTCTGTTGGCTGGGTGCCCAATACAACAAAAAGGCAGAGGAAAGGCAAATTCTTCTCTCCTCTGGAGCTGAGACACTCTTCTTCTTCTGCCCTTGGACATCAGAACTCCTGGCTCTCCGGCCTTTGAACTTCAGGACTTGTACCAGGAGGCCCTGGGTTCTCAGGCCTTTGGCTTTGGACTGAGAGTTACACAATCAGCTTCCCTGGTTCTGAGGCTTTCAGACTTAAACTGAGCCATGCTACCAGCATCCCAGGGTCTCCAGCCTACAGATGAGCTGTTGTGCGATTTCTTAGCCTCCATAATCACATGAGCCAATCTCCTTAATAAATGCCTGCTCATAGATCTGTATCTACATCTATATCTGTATGTGCATCTATATCTATGCCTATATCTATATCTATATCATATTGATTTTGTCTCTCTGGAGAACCCTGACTAATAAAATGAGGCATCTAAAA (SEQ ID NO: 101) >NP_008926.2 butyrophilin subfamily 2 member A2isoform a precursor [Homo sapiens]MEPAAALHFSLPASLLLLLLLLLLSLCALVSAQFTVVGPANPILAMVGENTTLRCHLSPEKNAEDMEVRWFRSQFSPAVFVYKGGRERTEEQMEEYRGRITFVSKDINRGSVALVIHNVTAQENGIYRCYFQEGRSYDEAILRLVVAGLGSKPLIEIKAQEDGSIWLECISGGWYPEPLTVWRDPYGEVVPALKEVSIADADGLFMVTTAVIIRDKYVRNVSCSVNNTLLGQEKETVIFIPESFMPSASPWMVALAVILTASPWMVSMTVILAVFIIFMAVSICCIKKLQREKKILSGEKKVEQEEKEIAQQLQEELRWRRTFLHAADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVERKGEVLLIPQNGFWTLEMFGNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFTVPVRPFFRLGSDDSPIFICPALTGASGVMVPEEGLKLHRVGTHQSL (SEQ ID NO: 102) Mouse>NM_175938.3 Mus musculus butyrophilin, subfamily 2, BTN2A2member A2 (Btn2a2), transcript variant 1, mRNAGAAATTGTGAGACTTGCACGCGGAATGGGTCCTCCGAGGTCTGCTGTCGCGAGTCCCAGCACTTTGCAAGTAATGGAGAACAGAAAATTCTTTCCTCTCTACTGTAGCAGTTTGTTCTCTGGTGGCGACTGTGCTCAGCGACAAGTTGGAGAGTAGAGAAAAGGCAAGATAATCAGCATTTGAGGGTCAGAGAAGAAAAGAAAACGCAGTTAATTCTAGAAGGTTTTCTGTCCACACGTGACCTAGGTGACTCTGTCCTGAAGACCTATGGAGCCTACAACTTCCCTGCGTTCTTGCCCGATAGCCTCCCTTCTCTTCTTCTTGGTCCTCAGCCTGTTTGTGCTGGTCTCAGCCCAGTTTACTGTCATAGGACCAGCTGAGCCCATCCTGGCCATGGTAGGAGAGAATACCACACTACACTGCCACCTGTCACCAGAGAGAAATGCCGAAGAGATGGAGGTGCGGTGGTTCCGGTGGCGTTTCTTCCCTGCAGTGCTGGTGTACAGAGGCCATCAAGAGAGACCAGAGGAGCAGATGGTGGCATACCGAGGAAGAACCACCTTCATGCGCACAGACATCAGCAAGGGAAGAGTTGCGCTCATTATCCACAATGTCACAGCCTATGACAATGGCATCTACTGCTGTTACTTCCAGGAAGGCAGGTCCTATGACCAGGCAACCATGAAGCTTATGGTGGCAAGCCTTGGCTCTGAGCCACTTATTAAAATGAAGACACTTGAGGATGGGAGCATCTTGCTAGAGTGCACATCTGAAGGGTGGTACCCAGAGCCCCGAGCTGTGTGGAGAGACCCCTATGATGAAGTTGTACCTGCCCTGGAGGAGGAGTATACAGCTGACAGAGAAGGCCTCTTCACAGTCACCATGACTATAATCATCAGGGACTGCTCTGTGAGGAACATGACCTGCTCTGTCAATAACACTCTGCTCAGCCAGGAGGTGGAAAGTGTGATTCTCATTCCAGAATCCTTCGTGCCCAGCCTTCCTCTGTGGATGGTGGCTGTGGCTGTCACTCTGCCTGTAGTAATGCTGATTCTCCTCACATCTGGAAGCATCTGCCTTGTCAAGAAACACCGCAGGAAGAAATCTATTCTGTCAGCTGAAAAAGAAGCCGAATATGAAGAGAAGGAAGCTGCACGGCAACTTCAAGAGGAACTGCGATGGAGACGAACCCTCTTACATGCTGCTGACGTGGTCCTGGACCCAGATACAGCTCATCCTGAGCTCTTCCTGTCAGATGACCAGAGAAGTGTAATACGAGGCTCTTCGAGGCAGAGTGTGCCTGACAACCCTGAGAGATTTGACTGCCGTCCATGTGTCCTGGGCAGGGAAAGCTTCTCCTCAGGGAAGCATTACTGGGAGGTGGAGGTGGAAAATGTAATGGTGTGGGCCATTGGTGTTTGTAGAGACAGCGTGGAAAGGAAAGGGGAGGCCCTGTTGGTTCCTCAGAATGGCTTCTGGACCCTGGAGATGTTTGGAAGCCAGTATCGAGCCCTGTCCTCCCCAGAAAAGATCATACCTCTGAAAGAGCGTCTTCACCGTATAGCTGTCTTCCTGGACTGTGAGGGTGGAGATATTTCTTTCTACAACATGAGAGACAGATCACACATTTACACATGTCCTCCTGTGACTTTCACTGGGCCCCTGAGACCCTTCTTTAGGCTTGGTTCTGATGACAGTCCCCTGTTCATCTGTCCAGCATTCACAGGGGCACAGGGAGTTACAATACCTGAGGGTGGCTTATTCCTATATAAGACAAGACCAATTTCTCAGAGCCTTGTAAGGAAGCCATAGCTCTCTACACAGTACCATCTGTTGGAGACTAGACCCCATGTCCTTCAGATCACATGGAGCATCTTCCAGCTGCCACCTTCACACATACTTCAGGCCCAGTCCTCAGATTACTACATCATTTCTTCTAACTATGGGCCTAGGTAGAGCCAGTCTTAGGGGACTATTGCTGTAATACAGCTCTCTCCTGAGAAGAAAGTGTGAGAAGGGCAGAAAACTTGGAGTTTCAACATGCTGCTCTGGTCACAGTGGATATCAGGCAAGAGCAACAGGGTGGATCAGGATGTAAGAAGTGAGAACTACAGAGGAAGGAGACAGATAAAGATGAATTGAGGCCGAAGATGGAGGAAATGGACTGAAGAGCTCTGGGGTAAGCCCTATGTGACAGCTGTGGATAGGTAGGAGCTAATGGTCCATTGATATCCAAAGCCAAAGATTTAAATATCACATAGTGTGTCTGGAGTGTATATCTGTAGACCTACACATGAGAGGAAACAATCATAGTGATGAACTGGATGTAAGCTGGCTCAGACGTCCCTACAATAAACACTTCTGAGTTCCATGTCTGTGCTCAGTAAGAATGGCTTGAGGCTTGCGGTCCATGCTGAGCAGCCAGGTCCACATGAATCGGATTTACTAGAGTAGGTAGCAGTTCAAGTTCCTTAGGCTCAGGATGTCTTCCTTTCCCCCAAGCCCTTCCCCCTTCAAGATAGGTCTCACTATGTAGACCAGGCCAGCCTCCACCTCCAGAGTTCTGGGATTAAAGACAAGCACAACCATGTCCAGTTTATGAGCTTGTGATATATACAGAAGATTAAGTTCTGTGTTCTTGGGTTAGTAACTGTTGAGATTTGTTTTGAGTCATGCTCTCACTGGCTAGCACTGCTCTTGACTTTCTCTCCCCATCTTTTTGTTATTGCTTTTCAAGACATGGTTTCACTGTGTATTTCTGGCTGATAAGCTGATTTTGAATTCACAGAGATCTGCCTCTGCCTCCTGAGTGCTGGGATTAAAGGTGTGTTACACTACGCCTGGCTTCACTCTATCTCTTCAGTGTGGGGATTATAGGTTTATACTATCATGCCTAACTAATGTCTGTTGCTGCATATGACATTTGAACTTTAGAACAGAAAAACAACTATACATATTAATATATATTAAACTAATAATAAGC (SEQ ID NO: 103) >NP_787952.2 butyrophilin subfamily 2 member A2isoform 1 precursor [Mus musculus]MEPTTSLRSCPIASLLFFLVLSLFVLVSAQFTVIGPAEPILAMVGENTTLHCHLSPERNAEEMEVRWFRWRFFPAVLVYRGHQERPEEQMVAYRGRTTFMRTDISKGRVALIIHNVTAYDNGIYCCYFQEGRSYDQATMKLMVASLGSEPLIKMKTLEDGSILLECTSEGWYPEPRAVWRDPYDEVVPALEEEYTADREGLFTVTMTIIIRDCSVRNMTCSVNNTLLSQEVESVILIPESFVPSLPLWMVAVAVTLPVVMLILLTSGSICLVKKHRRKKSILSAEKEAEYEEKEAARQLQEELRWRRTLLHAADVVLDPDTAHPELFLSDDQRSVIRGSSRQSVPDNPERFDCRPCVLGRESFSSGKHYWEVEVENVMVWAIGVCRDSVERKGEALLVPQNGFWTLEMFGSQYRALSSPEKIIPLKERLHRIAVFLDCEGGDISFYNMRDRSHIYTCPPVTFTGPLRPFFRLGSDDSPLFICPAFTGAQGVTIPEGGLFLYKTRPISQSLVRKP(SEQ ID NO: 104) Human>NM_001732.3 Homo sapiens butyrophilin subfamily 1 BTN1A1member A1 (BTN1A1), mRNAAGCTTTCTCACTTGGTAGCAGTGGCCTCTTGTGCCTTTTTCTCCAAGATCACCCAGGCTGAAGCTCCTGAGGGGACTCACATCAGTTATCTTGCTGCTCCAGAAGGGTGGGAGATGGCAGTTTTCCCAAGCTCCGGTCTCCCCAGATGTCTGCTCACCCTCATTCTCCTCCAGCTGCCCAAACTGGATTCAGCTCCCTTTGACGTGATTGGACCCCCGGAGCCCATCCTGGCCGTTGTGGGTGAGGACGCCGAGCTGCCCTGTCGCCTGTCTCCGAACGCGAGCGCCGAGCACTTGGAGCTACGCTGGTTCCGAAAGAAGGTTTCGCCGGCCGTGCTGGTGCATAGGGACGGGCGCGAGCAGGAAGCCGAGCAGATGCCCGAGTACCGCGGGCGGGCGACGCTGGTCCAGGACGGCATCGCCAAGGGGCGCGTGGCCTTGAGGATCCGTGGCGTCAGAGTCTCTGACGACGGGGAGTACACGTGCTTTTTCAGGGAGGATGGAAGCTACGAAGAAGCCCTGGTGCATCTGAAGGTGGCTGCTCTGGGCTCTGACCCTCACATCAGTATGCAAGTTCAAGAGAATGGAGAAATCTGTCTGGAGTGCACCTCAGTGGGATGGTACCCAGAGCCCCAGGTGCAGTGGAGAACTTCCAAGGGAGAGAAGTTTCCATCTACATCAGAGTCCAGGAATCCTGATGAAGAAGGTTTGTTCACTGTGGCTGCTTCAGTGATCATCAGAGACACTTCTGCGAAAAATGTGTCCTGCTACATCCAGAATCTCCTTCTTGGCCAGGAGAAGAAAGTAGAAATATCCATACCAGCTTCCTCCCTCCCAAGGCTGACTCCCTGGATAGTGGCTGTGGCTGTCATCCTGATGGTTCTAGGACTTCTCACCATTGGGTCCATATTTTTCACTTGGAGACTATACAACGAAAGACCCAGAGAGAGGAGGAATGAATTCAGCTCTAAAGAGAGACTCCTGGAAGAACTCAAATGGAAAAAGGCTACCTTGCATGCAGTTGATGTGACTCTGGACCCAGACACAGCTCATCCCCACCTCTTTCTTTATGAGGATTCAAAATCTGTTCGACTGGAAGATTCACGTCAGAAACTGCCTGAGAAAACAGAGAGATTTGACTCCTGGCCCTGTGTGTTGGGCCGTGAGACCTTCACCTCAGGAAGGCATTACTGGGAGGTGGAGGTGGGAGACAGGACTGACTGGGCAATCGGCGTGTGTAGGGAGAATGTGATGAAGAAAGGATTTGACCCCATGACTCCTGAGAATGGGTTCTGGGCTGTAGAGTTGTATGGAAATGGGTACTGGGCCCTCACTCCTCTCCGGACCCCTCTCCCATTGGCAGGGCCCCCACGCCGGGTTGGGATTTTCCTAGACTATGAATCAGGAGACATCTCCTTCTACAACATGAATGATGGATCTGATATCTATACTTTCTCCAATGTCACTTTCTCTGGCCCCCTCCGGCCCTTCTTTTGCCTATGGTCTAGCGGTAAAAAGCCCCTGACCATCTGCCCAATTGCTGATGGGCCTGAGAGGGTCACAGTCATTGCTAATGCCCAGGACCTTTCTAAGGAGATCCCATTGTCCCCCATGGGGGAGGACTCTGCCCCTAGGGATGCAGACACTCTCCATTCTAAGCTAATCCCTACCCAACCCAGCCAAGGGGCACCTTAAGGAATATCTCAGCTCATCTGTTTTCCTTTCCTCTAACCCCTCTCCTCCATAGCCTTCTGAGGCTTCACCTGCTAGCTTTACCCAGTCTGTTTCTTCCTGTTGGGTGGCAATTAATTAATCCTGTGAAGGTTACATTGCTGCTGCTAGAGAGGGTGGGGATTGCACCTTCCAAATCTGTTTCTGTACCAATATTTGGGGGATGGAGGGGTGACTCAAACTGCTTCTAGTGTTCTCCTAATCCCTTAAGACTAGAACCTATAGGAAACTACTTGGAGCAAACTCAAAGGACAGATTAGGGATCGAGATTGGGTCAGGTTAGCATGGGGTTGTGGTTGAAATATCTTGGTATCCAGGATAAGGGTATGTGGAAAAACAGGCTTTAGGCAAGTGGAAAATTCAAAATGTGCTGTGAAAGGACAATCTCAGGCTGAAATCCCATAAAGGAACTTGGAGGGAATATTATGATGGAGGGAAGTGAGGTGAATCCAGGCACATGATGAACACCTGGCTCATCCATAGAGTTTTCACAGCCTATATCGCAAATTTTCTAAGCCACGTCCTATAGGACAGAGGAGACTGGCCCCACTTCTATGGGTCTGAGCTGTGGAAAAGGGAGAGCAGAGAGGAACTGAGATGAGCAGGGATGAAGGGTCAGGCAGAAAGCGTGATAGAGGAGAGAATTTTTGACAAAACTCAAAAGTTGTTTGCACAGCTGTTCTTTGTACCCTGTTCCTTTCTCTGCGCCCTCCTGTTTCTCCCTTGCCTGGAAGTCATTCCACCCTCAATTTGTTGATCCACAAGTTTCCAGTTGTCCTCTTCTTTTTGTTATAGCATCTCTCTATTTCAAAGACATTCCTAGAAGTCATCCTTCAGTGATATCACCACTTGCTCAGTCACCATCTCAACCTTATGTCACCTCAGCCCTCATCTCAATGCCCAAACCCCTTACACACACCTTCAGTTAGCTTCAACTGCCTCCGTTTCCACACTGTGCACCTTTCACTTTCCCTACCCAGCTTTCCTACATGCTGCCTCTCCTCAGGGTCCCCTGAATGCTGCATCATTGTGTTCAGTGCAGCTGGACTGATTGCACCTGTGTATTTGCCCCTGAGCACTTTCCTTTACACATGTGGCTTGTCTTGCCAATAGACTCCAGGCTTATACCTTCCATTTCCATCGTATTCTCCAGTTTCCAGGATAGACGTTGCTCATCGTCTTTACCTAATAAATAAGTTTGTCTGATTGCTGAAA (SEQ ID NO: 105) >NP_001723.2 butyrophilin subfamily 1 member A1precursor [Homo sapiens]MAVFPSSGLPRCLLTLILLQLPKLDSAPFDVIGPPEPILAVVGEDAELPCRLSPNASAEHLELRWFRKKVSPAVLVHRDGREQEAEQMPEYRGRATLVQDGIAKGRVALRIRGVRVSDDGEYTCFFREDGSYEEALVHLKVAALGSDPHISMQVQENGEICLECTSVGWYPEPQVQWRTSKGEKFPSTSESRNPDEEGLFTVAASVIIRDTSAKNVSCYIQNLLLGQEKKVEISIPASSLPRLTPWIVAVAVILMVLGLLTIGSIFFTWRLYNERPRERRNEFSSKERLLEELKWKKATLHAVDVTLDPDTAHPHLFLYEDSKSVRLEDSRQKLPEKTERFDSWPCVLGRETFTSGRHYWEVEVGDRTDWAIGVCRENVMKKGFDPMTPENGFWAVELYGNGYWALTPLRTPLPLAGPPRRVGIFLDYESGDISFYNMNDGSDIYTFSNVTFSGPLRPFFCLWSSGKKPLTICPIADGPERVTVIANAQDLSKEIPLSPMGEDSAPRDADTLHSKLIPTQPSQGAP (SEQ ID NO: 106) Mouse>NM_013483.3 Mus musculus butyrophilin, subfamily 1, BTN1A1member A1 (Btn1a1), mRNAAACAGCACACAGCCTTCTTCCTTCTGAAGAGCTCTCTCTTTGGCCCCGGGGTGACAAGCAGCCCTTTTCACTTGATCACTGTGGCTCTGGCTCCCTTTTCCTCTGGGTCTGTCGAAATCGCCTGAAGCTCTTGGCGGGCTTCATTGCCCCAGTTAGCTCAGAGATGGCAGTTCCCACCAACTCCTGCCTCCTGGTCTGTCTGCTCACCCTCACTGTCCTACAGCTGCCCACGCTGGATTCGGCAGCTCCCTTCGATGTGACCGCACCTCAGGAGCCAGTGTTGGCCCTAGTGGGCTCAGATGCCGAGCTGACCTGTGGCTTTTCCCCAAACGCGAGCTCAGAATACATGGAGCTGCTGTGGTTTCGACAGACGAGGTCGACAGCGGTACTTCTATACCGGGATGGCCAGGAGCAGGAGGGCCAGCAGATGACGGAGTACCGCGGGAGGGCGACGCTGGCGACAGCCGGGCTTCTAGACGGCCGCGCTACTCTGCTGATCCGAGATGTCAGGGTCTCAGACCAGGGGGAGTACCGGTGCCTTTTCAAAGACAACGACGACTTCGAGGAGGCCGCCGTATACCTCAAAGTGGCTGCTGTGGGTTCAGATCCTCAAATCAGTATGACGGTTCAAGAGAATGGAGAAATGGAGCTGGAGTGCACCTCCTCTGGATGGTACCCAGAGCCTCAGGTGCAGTGGAGAACAGGCAACAGAGAGATGCTACCATCCACGTCAGAGTCCAAGAAGCATAATGAGGAAGGCCTGTTCACTGTGGCAGTTTCAATGATGATCAGAGACAGCTCCATAAAGAACATGTCCTGCTGCATCCAGAATATCCTCCTTGGCCAGGGGAAGGAAGTAGAGATCTCCTTACCAGCTCCCTTCGTGCCAAGGCTGACTCCCTGGATAGTAGCTGTGGCTATCATCTTACTGGCCTTAGGATTTCTCACCATTGGGTCCATATTTTTCACTTGGAAACTATACAAGGAAAGATCCAGTCTGCGGAAGAAGGAATTTGGCTCTAAAGAGAGACTTCTGGAAGAACTCAGATGCAAAAAGACTGTACTGCATGAAGTTGACGTGACTCTGGATCCAGACACAGCCCACCCCCACCTCTTCCTGTATGAAGATTCAAAGTCAGTTCGATTGGAAGATTCACGTCAGATCCTGCCTGATAGACCAGAGAGATTTGACTCCTGGCCCTGTGTGTTGGGCCGTGAGACCTTTACTTCAGGGAGACATTACTGGGAGGTGGAGGTGGGAGATAGAACTGACTGGGCCATTGGTGTGTGTAGGGAGAATGTGGTGAAGAAAGGGTTTGACCCCATGACTCCTGATAATGGGTTCTGGGCTGTGGAGTTGTATGGAAATGGGTACTGGGCCCTCACCCCACTCAGGACCTCTCTCCGATTAGCAGGGCCCCCTCGCAGAGTTGGGGTTTTTCTGGACTATGACGCAGGAGACATTTCCTTCTACAACATGAGTAACGGATCTCTTATCTATACTTTCCCTAGCATCTCTTTCTCTGGCCCCCTCCGTCCCTTCTTTTGTCTGTGGTCCTGTGGTAAAAAGCCCCTGACCATCTGTTCAACTGCCAATGGGCCTGAGAAAGTCACAGTCATTGCTAATGTCCAGGACGACATTCCCTTGTCCCCGCTGGGGGAAGGCTGTACTTCTGGAGACAAAGACACTCTCCATTCTAAACTGATCCCGTTCTCACCTAGCCAAGCGGCACCATAACAAATATTCCAGCTTCACGACTTTGCCTTCCTTTGACTAATCCCTCATGCCCCGAAGCTTCAGCTGTTGGCTTCTTGCAGCCCTGCTTCTTCCTGGTGGATGGAGATTAATTCACATTGGGAAGGTTAGGTATGTTGCTGCCAGACAAGGCAGGAAGAAAGGCCATCCTAGTTTGTTTCTGTACTAACAGTGGGGAGGAAGAGAGCTGAATCCTAAACTATTTCCAGTGCTCATATTCCTTCAGGCCAGAGCCTATAGAGAAGGATTTGGTACAATCACTCGAGGGATCAAGAGGCAATTAGGTTGGCATGGAATTATGGCAGAAACATCTGGAATAGGGGTATGTGGAATGACAGGTTTTAGGTAAGGGAGAACAAAACCAAACCATAGGATGCTGAGAAAGAAAGATCTTGGACTAAACTCCTAAAAAAGCACTTAGAGAAGATATGACAGGCAAATGAAGTGAATTTGGTCTAATTTGATACACTTGCCCTGTCCCTAGGGTTTTTCAGTTATATCTCAATTTTTTTGTTGTTAATTACATTTTTGACAGCTTCATACATGTATATAATGCATTCTAATTACTCTCACTCTCCTCTATTCTGTCTTATTTCCCTCCCCTCCCCTCATACCTTCCTTCTTGCTTCAAACCTGGCACACTGAGTTTAATGGGCTATCATGGGAACATGGATTTAGAGCTTTCCTCTGAGCTCAAGAGAGCAGGTGTGACTGAATACAGTGATTTCCCCTCTCCTACAATCAATCAGCAGTCAATAGCTCAGCTGGGAGGGGTAGGGCCTCATGAGACTTCCCCTATCAAGGCTAAATGTTGAAAGGGCCAGTTTTTAGCACCTGTGAGATCATGATTGCAAGAGCCCAGAAGACAGCATTGCTCGGTCATTCTCCCTACCCTTTGGCTTTTCTGGTOTTTTGTCCTCTCTTTCAGGATGTGTCTGAACTCTGTATCTTAAGTTTTCTATGTCATGTTCTATAAGATAGAGGAGACTGGCCCTGCTTGTTTGAGAGCAATGTGAGCAAGCTAGCAAGAGACAGAAAGGAGCGGAGATGAATAGGGGTAGAGAAAATTTTTAAACAAACCCTCCAGGTGTGTGTGTGTGTGTGTGTGTCTTCCTCTTTTTTGACCTCCCTAAAGGTCAATCCAACCTCACATTATTGACTCCACTAGGTGGGGGTTCTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTTTTAAGATAGAGGTTTACTATGTAGCTTAGGCTGGCTTTGAATTCCTGATCCTCCTGCCTCTACCTTCCAAGTGCTGGAAACATAGCCACATCCACCACCCCTATCCAGTCCACCTGGTTTGATTCAGCAACGCTCAGGTAGCATCGCTGTTTGATCTGGAGCTGCCAGCTCCCTCGGCCCCCACTGCAATGCTTAACCCCCTCACAGGCACCTTCCCTTGCCTAACACTGCCATCCTTTTCCACACTGAGCCATTTGCTCAATGTAGCCTACCCAGGTATCCTGCTTTCTGGTCCCCAAAGTTACACCATGATGCTCAGCACAGCTGGACAGTTTGTCCCAATTTGTGTGTGTCCTCCTGTTTGTATGGGACTTCTTTTTGTCAATGGCCTGTGTGTGTATCCAAGCTCTTCCACTTCTATTGTATTTTTCCGGCTTCTAAAACAGATGTTACCAAATAAAGAAAGAGAAAGAAAAAAAA (SEQ ID NO: 107) >NP_038511.1 butyrophilin subfamily 1 member A1precursor [Mus musculus]MAVPTNSCLLVCLLTLTVLQLPTLDSAAPFDVTAPQEPVLALVGSDAELTCGFSPNASSEYMELLWFRQTRSTAVLLYRDGQEQEGQQMTEYRGRATLATAGLLDGRATLLIRDVRVSDQGEYRCLFKDNDDFEEAAVYLKVAAVGSDPQISMTVQENGEMELECTSSGWYPEPQVQWRTGNREMLPSTSESKKHNEEGLFTVAVSMMIRDSSIKNMSCCIQNILLGQGKEVEISLPAPFVPRLTPWIVAVAIILLALGFLTIGSIFFTWKLYKERSSLRKKEFGSKERLLEELRCKKTVLHEVDVTLDPDTAHPHLFLYEDSKSVRLEDSRQILPDRPERFDSWPCVLGRETFTSGRHYWEVEVGDRTDWAIGVCRENVVKKGFDPMTPDNGFWAVELYGNGYWALTPLRTSLRLAGPPRRVGVFLDYDAGDISFYNMSNGSLIYTFPSISFSGPLRPFFCLWSCGKKPLTICSTANGPEKVTVIANVQDDIPLSPLGEGCTSGDKDTLHSKLIPFSPSQAAP (SEQ ID NO: 108)Human TIGIT >NM_173799.4 Homo sapiens T cell immunoreceptor withIg and ITIM domains (TIGIT), mRNAACATCTGCTTCCTGTAGGCCCTCTGGGCAGAAGCATGCGCTGGTGTCTCCTCCTGATCTGGGCCCAGGGGCTGAGGCAGGCTCCCCTCGCCTCAGGAATGATGACAGGCACAATAGAAACAACGGGGAACATTTCTGCAGAGAAAGGTGGCTCTATCATCTTACAATGTCACCTCTCCTCCACCACGGCACAAGTGACCCAGGTCAACTGGGAGCAGCAGGACCAGCTTCTGGCCATTTGTAATGCTGACTTGGGGTGGCACATCTCCCCATCCTTCAAGGATCGAGTGGCCCCAGGTCCCGGCCTGGGCCTCACCCTCCAGTCGCTGACCGTGAACGATACAGGGGAGTACTTCTGCATCTATCACACCTACCCTGATGGGACGTACACTGGGAGAATCTTCCTGGAGGTCCTAGAAAGCTCAGTGGCTGAGCACGGTGCCAGGTTCCAGATTCCATTGCTTGGAGCCATGGCCGCGACGCTGGTGGTCATCTGCACAGCAGTCATCGTGGTGGTCGCGTTGACTAGAAAGAAGAAAGCCCTCAGAATCCATTCTGTGGAAGGTGACCTCAGGAGAAAATCAGCTGGACAGGAGGAATGGAGCCCCAGTGCTCCCTCACCCCCAGGAAGCTGTGTCCAGGCAGAAGCTGCACCTGCTGGGCTCTGTGGAGAGCAGCGGGGAGAGGACTGTGCCGAGCTGCATGACTACTTCAATGTCCTGAGTTACAGAAGCCTGGGTAACTGCAGCTTCTTCACAGAGACTGGTTAGCAACCAGAGGCATCTTCTGGAAGATACACTTTTGTCTTTGCTATTATAGATGAATATATAAGCAGCTGTACTCTCCATCAGTGCTGCGTGTGTGTGTGTGTGTGTATGTGTGTGTGTGTTCAGTTGAGTGAATAAATGTCATCCTCTTCTCCATCTTCATTTCCTTGGCCTTTTCGTTCTATTCCATTTTGCATTATGGCAGGCCTAGGGTGAGTAACGTGGATCTTGATCATAAATGCAAAATTAAAAAATATCTTGACCTGGTTTTAAATCTGGCAGTTTGAGCAGATCCTATGTCTCTGAGAGACACATTCCTCATAATGGCCAGCATTTTGGGCTACAAGGTTTTGTGGTTGATGATGAGGATGGCATGACTGCAGAGCCATCCTCATCTCATTTTTTCACGTCATTTTCAGTAACTTTCACTCATTCAAAGGCAGGTTATAAGTAAGTCCTGGTAGCAGCCTCTATGGGGAGATTTGAGAGTGACTAAATCTTGGTATCTGCCCTCAAGAACTTACAGTTAAATGGGGAGACAATGTTGTCATGAAAAGGTATTATAGTAAGGAGAGAAGGAGACATACACAGGCCTTCAGGAAGAGACGACAGTTTGGGGTGAGGTAGTTGGCATAGGCTTATCTGTGATGAAGTGGCCTGGGAGCACCAAGGGGATGTTGAGGCTAGTCTGGGAGGAGCAGGAGTTTTGTCTAGGGAACTTGTAGGAAATTCTTGGAGCTGAAAGTCCCACAAAGAAGGCCCTGGCACCAAGGGAGTCAGCAAACTTCAGATTTTATTCTCTGGGCAGGCATTTCAAGTTTCCTTTTGCTGTGACATACTCATCCATTAGACAGCCTGATACAGGCCTGTAGCCTCTTCCGGCCGTGTGTGCTGGGGAAGCCCCAGGAAACGCACATGCCCACACAGGGAGCCAAGTCGTAGCATTTGGGCCTTGATCTACCTTTTCTGCATCAATACACTCTTGAGCCTTTGAAAAAAGAACGTTTCCCACTAAAAAGAAAATGTGGATTTTTAAAATAGGGACTCTTCCTAGGGGAAAAAGGGGGGCTGGGAGTGATAGAGGGTTTAAAAAATAAACACCTTCAAACTAACTTCTTCGAACCCTTTTATTCACTCCCTGACGACTTTGTGCTGGGGTTGGGGTAACTGAACCGCTTATTTCTGTTTAATTGCATTCAGGCTGGATCTTAGAAGACTTTTATCCTTCCACCATCTCTCTCAGAGGAATGAGCGGGGAGGTTGGATTTACTGGTGACTGATTTTCTTTCATGGGCCAAGGAACTGAAAGAGAATGTGAAGCAAGGTTGTGTCTTGCGCATGGTTAAAAATAAAGCATTGTCCTGCTTCCTAAGACTTAGACTGGGGTTGACAATTGTTTTAGCAACAAGACAATTCAACTATTTCTCCTAGGATTTTTATTATTATTATTTTTTCACTTTTCTACCAAATGGGTTACATAGGAAGAATGAACTGAAATCTGTCCAGAGCTCCAAGTCCTTTGGAAGAAAGATTAGATGAACGTAAAAATGTTGTTGTTTGCTGTGGCAGTTTACAGCATTTTTCTTGCAAAATTAGTGCAAATCTGTTGGAAATAGAACACAATTCACAAATTGGAAGTGAACTAAAATGTAATGACGAAAAGGGAGTAGTGTTTTGATTTGGAGGAGGTGTATATTCGGCAGAGGTTGGACTGAGAGTTGGGTGTTATTTAACATAATTATGGTAATTGGGAAACATTTATAAACACTATTGGGATGGTGATAAAATACAAAAGGGCCTATAGATGTTAGAAATGGGTCAGGTTACTGAAATGGGATTCAATTTGAAAAAAATTTTTTTAAATAGAACTCACTGAACTAGATTCTCCTCTGAGAACCAGAGAAGACCATTTCATAGTTGGATTCCTGGAGACATGCGCTATCCACCACGTAGCCACTTTCCACATGTGGCCATCAACCACTTAAGATGGGGTTAGTTTAAATCAAGATGTGCTGTTATAATTGGTATAAGCATAAAATCACACTAGATTCTGGAGATTTAATATGAATAATAAGAATACTATTTCAGTAGTTTTGGTATATTGTGTGTCAAAAATGATAATATTTTGGATGTATTGGGTGAAATAAAATATTAACATTA (SEQ ID NO: 109) >NP_776160.2 T-cell immunoreceptor with Ig and ITIMdomains precursor [Homo sapiens]MRWCLLLIWAQGLRQAPLASGMMTGTIETTGNISAEKGGSIILQCHLSSTTAQVTQVNWEQQDQLLAICNADLGWHISPSFKDRVAPGPGLGLTLQSLTVNDTGEYFCIYHTYPDGTYTGRIFLEVLESSVAEHGARFQIPLLGAMAATLVVICTAVIVVVALTRKKKALRIHSVEGDLRRKSAGQEEWSPSAPSPPGSCVQAEAAPAGLCGEQRGEDCAELHDYFNVLSYRSLGNCSFFTETG (SEQ ID NO: 110) Mouse TIGIT>NM_001146325.1:98-823 Mus musculus T cellimmunoreceptor with Ig and ITIM domains (Tigit), mRNAATGCATGGCTGGCTGCTCCTGGTCTGGGTCCAGGGGCTGATACAGGCTGCCTTCCTCGCTACAGGAGCCACAGCAGGCACGATAGATACAAAGAGGAACATCTCTGCAGAGGAAGGTGGCTCTGTCATCTTACAGTGTCACTTCTCCTCTGACACAGCTGAAGTGACCCAAGTCGACTGGAAGCAGCAGGACCAGCTTCTGGCCATTTATAGTGTTGACCTGGGGTGGCATGTCGCTTCAGTCTTCAGTGATCGGGTGGTCCCAGGCCCCAGCCTAGGCCTCACCTTCCAGTCTCTGACAATGAATGACACGGGAGAGTACTTCTGTACCTATCATACGTATCCTGGTGGGATTTACAAGGGGAGAATATTCCTGAAGGTCCAAGAAAGCTCAGTGGCTCAGTTCCAGACTGCCCCGCTTGGAGGAACCATGGCTGCTGTGCTGGGACTCATTTGCTTAATGGTCACAGGAGTGACTGTACTGGCTAGAAAGAAGTCTATTAGAATGCATTCTATAGAAAGTGGCCTTGGGAGAACAGAAGCGGAGCCACAGGAATGGAACCTGAGGAGTCTCTCATCCCCTGGAAGCCCTGTCCAGACACAAACTGCCCCTGCTGGTCCCTGTGGAGAGCAGGCAGAAGATGACTATGCTGACCCACAGGAATACTTTAATGTCCTGAGCTACAGAAGCCTAGAGAGCTTCATTGCTGTATCGAAGACTGGCTAA (SEQ ID NO: 111) >NP_001139797.1 T-cell immunoreceptor with Ig andITIM domains precursor [Mus musculus]MHGWLLLVWVQGLIQAAFLATGATAGTIDTKRNISAEEGGSVILQCHFSSDTAEVTQVDWKQQDQLLAIYSVDLGWHVASVFSDRVVPGPSLGLTFQSLTMNDTGEYFCTYHTYPGGIYKGRIFLKVQESSVAQFQTAPLGGTMAAVLGLICLMVTGVTVLARKKSIRMHSIESGLGRTEAEPQEWNLRSLSSPGSPVQTQTAPAGPCGEQAEDDYADPQEYFNVLSYRSLESFIAVSKTG (SEQ ID NO: 112) Human>NM_001252.5 Homo sapiens CD70 molecule (CD70), CD27L (CD70)transcript variant 1, mRNAAGAGAGGGGCAGGCTGGTCCCCTGACAGGTTGAAGCAAGTAGACGCCCAGGAGCCCCGGGAGGGGGCTGCAGTTTCCTTCCTTCCTTCTCGGCAGCGCTCCGCGCCCCCATCGCCCCTCCTGCGCTAGCGGAGGTGATCGCCGCGGCGATGCCGGAGGAGGGTTCGGGCTGCTCGGTGCGGCGCAGGCCCTATGGGTGCGTCCTGCGGGCTGCTTTGGTCCCATTGGTCGCGGGCTTGGTGATCTGCCTCGTGGTGTGCATCCAGCGCTTCGCACAGGCTCAGCAGCAGCTGCCGCTCGAGTCACTTGGGTGGGACGTAGCTGAGCTGCAGCTGAATCACACAGGACCTCAGCAGGACCCCAGGCTATACTGGCAGGGGGGCCCAGCACTGGGCCGCTCCTTCCTGCATGGACCAGAGCTGGACAAGGGGCAGCTACGTATCCATCGTGATGGCATCTACATGGTACACATCCAGGTGACGCTGGCCATCTGCTCCTCCACGACGGCCTCCAGGCACCACCCCACCACCCTGGCCGTGGGAATCTGCTCTCCCGCCTCCCGTAGCATCAGCCTGCTGCGTCTCAGCTTCCACCAAGGTTGTACCATTGCCTCCCAGCGCCTGACGCCCCTGGCCCGAGGGGACACACTCTGCACCAACCTCACTGGGACACTTTTGCCTTCCCGAAACACTGATGAGACCTTCTTTGGAGTGCAGTGGGTGCGCCCCTGACCACTGCTGCTGATTAGGGTTTTTTAAATTTTATTTTATTTTATTTAAGTTCAAGAGAAAAAGTGTACACACAGGGGCCACCCGGGGTTGGGGTGGGAGTGTGGTGGGGGGTAGTGGTGGCAGGACAAGAGAAGGCATTGAGCTTTTTCTTTCATTTTCCTATTAAAAAATACAAAAATCA (SEQ ID NO: 113)>NP_001243.1 CD70 antigen isoform 1 [Homo sapiens]MPEEGSGCSVRRRPYGCVLRAALVPLVAGLVICLVVCIQRFAQAQQQLPLESLGWDVAELQLNHTGPQQDPRLYWQGGPALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAICSSTTASRHHPTTLAVGICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLPSRNTDETFFGVQWVRP (SEQ ID NO: 114) Mouse CD27L>NM_011617.2 Mus musculus CD70 antigen (Cd70), mRNA (CD70)GAAGGTGCCAAAAGCTCCAGGGGATTTCCCTGCCCTCCGAGAAGAGGCCCAGTTCTTCCCCTGCATCGGACATCCCCGAGGTTCTAAGGGCAGGTCAAGGCAGGCAGAAGCTTCAAAAGCTCGGCTGAGGAGGCTACAGCTTCCCGCTGCCTTCAGGCCGCTGCTTCCGTGCAGGGATGCCGGAGGAAGGTCGCCCTTGCCCCTGGGTTCGCTGGAGCGGGACCGCGTTCCAGCGCCAATGGCCATGGCTGCTGCTGGTGGTGTTTATTACTGTGTTTTGCTGTTGGTTTCATTGTAGCGGACTACTCAGTAAGCAGCAACAGAGGCTGCTGGAGCACCCTGAGCCGCACACAGCTGAGTTACAGCTGAATCTCACAGTTCCTCGGAAGGACCCCACACTGCGCTGGGGAGCAGGCCCAGCCTTGGGAAGGTCCTTCACACACGGACCAGAGCTGGAGGAGGGCCATCTGCGTATCCATCAAGATGGCCTCTACAGGCTGCATATCCAGGTGACACTGGCCAACTGCTCTTCCCCAGGCAGCACCCTGCAGCACAGGGCCACCCTGGCTGTGGGCATCTGCTCCCCCGCTGCGCACGGCATCAGCTTGCTGCGTGGGCGCTTTGGACAGGACTGTACAGTGGCATTACAGCGCCTGACATACCTGGTCCACGGAGATGTCCTCTGTACCAACCTCACCCTGCCTCTGCTGCCGTCCCGCAACGCTGATGAGACCTTCTTTGGAGTTCAGTGGATATGCCCTTGACCACAACTCCAGGATGACTTGTGAATATTTTTTTTCTTTTCAAGTTCTACGTATTTATAAATGTATATAGTACACATA (SEQ ID NO: 115)>NP_035747.1 0D70 antigen [Mus musculus]MPEEGRPCPWVRWSGTAFQRQWPWLLLVVFITVFCCWFHCSGLLSKQQQRLLEHPEPHTAELQLNLTVPRKDPTLRWGAGPALGRSFTHGPELEEGHLRIHQDGLYRLHIQVTLANCSSPGSTLQHRATLAVGICSPAAHGISLLRGRFGQDCTVALQRLTYLVHGDVLCTNLTLPLLPSRNADETFFGVQWICP (SEQ ID NO: 116) Human>NM_001244.4 Homo sapiens TNF superfamily member 8 CD30L(TNFSF8), transcript variant 1, mRNA (CD153)GTCATTTTCCTACGCGCCCTCTGACATCAGCCACCTTCTCTGTAGCTAGTTTCTCTGCACACAACTTAATCCCTGGCAATGAAAAATGAACCTCTCCCCCACCCTTGCTGCCGCCTCTCGCCTCACGCCCCCAGAGAAGAGTTTCTCCACCAGGCAGCAGGTGAAGGTTTTTTTCCAAGTCACATGATTCAGGATTCAGGGGGAGAATCCTTCTTGGAACAGAGATGGGCCCAGAACTGATCAGATGAAGAGAGATAAGGTGTGATGTGGGGAAGACTATATAAAGAATGGACCCAGGGCTGCAGCAAGCACTCAACGGAATGGCCCCTCCTGGAGACACAGCCATGCATGTGCCGGCGGGCTCCGTGGCCAGCCACCTGGGGACCACGAGCCGCAGCTATTTCTATTTGACCACAGCCACTCTGGCTCTGTGCCTTGTCTTCACGGTGGCCACTATTATGGTGTTGGTCGTTCAGAGGACGGACTCCATTCCCAACTCACCTGACAACGTCCCCCTCAAAGGAGGAAATTGCTCAGAAGACCTCTTATGTATCCTGAAAAGGGCTCCATTCAAGAAGTCATGGGCCTACCTCCAAGTGGCAAAGCATCTAAACAAAACCAAGTTGTCTTGGAACAAAGATGGCATTCTCCATGGAGTCAGATATCAGGATGGGAATCTGGTGATCCAATTCCCTGGTTTGTACTTCATCATTTGCCAACTGCAGTTTCTTGTACAATGCCCAAATAATTCTGTCGATCTGAAGTTGGAGCTTCTCATCAACAAGCATATCAAAAAACAGGCCCTGGTGACAGTGTGTGAGTCTGGAATGCAAACGAAACACGTATACCAGAATCTCTCTCAATTCTTGCTGGATTACCTGCAGGTCAACACCACCATATCAGTCAATGTGGATACATTCCAGTACATAGATACAAGCACCTTTCCTCTTGAGAATGTGTTGTCCATCTTCTTATACAGTAATTCAGACTGAACAGTTTCTCTTGGCCTTCAGGAAGAAAGCGCCTCTCTACCATACAGTATTTCATCCCTCCAAACACTTGGGCAAAAAGAAAACTTTAGACCAAGACAAACTACACAGGGTATTAAATAGTATACTTCTCCTTCTGTCTCTTGGAAAGATACAGCTCCAGGGTTAAAAAGAGAGTTTTTAGTGAAGTATCTTTCAGATAGCAGGCAGGGAAGCAATGTAGTGTGGTGGGCAGAGCCCCACACAGAATCAGAAGGGATGAATGGATGTCCCAGCCCAACCTCTAATTCACTGTATGGTCTTGATCTATTTCTTCTGTTTTGAGAGCCTCCAGTTAAAATGGGGCTCCAGTACCAGAGCAGCTAGCAACTCTGCCCTAATGGGAAATGAAGGGGAGCTGGGTGTGAGTGTTTACACTGTGCCCTTCACGGGATACTTCTTTTATCTGCAGATGGCCTAATACTTAGTTGTCCAAGTCGCGATCAAGGACTCTCTCACACAGGAAACTTCCCTATACTGGCAGATACACTTGTGACTGAACCATGCCCAGTTTATGCCTGTCTGACTGTCACTCTGGCACTAGGAGGCTGATCTTGTACTCCATATGACCCCACCCCTAGGAACCCCCAGGGAAAACCAGGCTGGGACAGCCCCCTGTTCCTGAGATGGAAAGCACAAATTTAATACACCACCACAATGGAAAACAAGTTCAAAGACTTTTACTTACAGATCCTGGACAGAAAGGGCATAATGAGTCTGAAGGGCAGTCCTCCTTCTCTAGGTTACATGAGGCAGGAATAAGAAGTCAGACAGAGACAGCAAGACAGTTAACAATGTAGGTAAAGAAATAGGGTGTGGTCACTCTCAATTCACTGGCAAATGCCTGAATGGTCTGTCTGAAGGAAGCAACAGAGAAGTGGGGAATCCAGTCTGCTAGGCAGGAAAGATGCCTCTAAGTTCTTGTCTCTGGCCAGAGGTGTGGTATAGAACCAGAAACCCATATCAAGGGTGACTAAGCCCGGCTTCTGGTATGAGAAATTAAACTTGTATACAAAATGGTTGCCAAGGCAACATAAAATTATAAGAATTCACTATACCTTCCCCTCCCTGGAACTCAGGATCCAAGTCTAGAAAATGAAAGGACTGGGTTTGAATTGCTTCAAAACCTCTTCCATCTCAGAAGACCAGACCCTGGGAACTGAGATTCCAGACACAATTTTGGAAGCTCTCCAACCAAAATAAGGCCCCCCTACCCCAGTATATAATTGAAGACACTAGTAACACCTGACTGCATCTCATCTCAGCAGAGCCAGAATATGGGGACAAGGTTCAGGGTGCCCTGCTGAATGGTGTGAACAGCAGGATCTCAAGGATGTAATGGAAAGAACTACCACACTGACCATCCAGAATCTAAGAGACCATCTGGGTGTTTGGGAAACCATCTGACGAGGCCTGACTCTATTCCAGTTAGATTGACAATAATTGAGCAGCAGGCATTTTTCATTTCTGGTCAGGAAAGCATTGTGCCTTTAGCAAACAATCAGTGTGCAACAGTGATGTGGTCATCTAGCCAGGGAATGGCTGCTCCATCCCCTGCATAATATATTCCTGCTTCAAACACCTCTCAGAAAACCAGTTCCGCGAGGGTTTTTATATCCCCACAAAGTTGTTGAGAGACAATGATGACCCTGGAAGTGGGGAGGAGGACTTCTGAGAAACAGCAACCTCTCTCCTGATTGGGGTAGCCATGAGATTTCTCTAGCTATATCCAACTTGGCATCTGTACATCATCTTTGGAGGAACATCTTATTTGTGGAAGGACCTTGACAAGCCGTTTGAGATGGAATGTAGGCCCTGATGTTATGCTTCAGTAAAAAAAGATGGAAGCTTCCCTGCTATACCAAAACATGGAGCAAAATTTGCATTTTTCTCAAGAAGGAGAGAAAAGGAGTAGGACTCCAGCAAAGTTTGTCAGAAGGAAAGCTAGAAAAGATTTAAAAGAAAAAAAGAAAGAACAAATCAGCAGTGGTGGTATGGATGAAAGGGACTTGAGAGAACAAAAATGGCTAAGGGAAAATTTTAAGTCATCTGCTGAGCAGTGTGCTGTGTCAACCTCCTCCTAGGTCTCCTCTATGAAATATTTAGTAAAGTCTACATTTCTCTTTAACTCTTTCTGTGAGTAGATTCTTTGGGAGAAGCAGGCATTGGAAGAGGTGTTGAATTCAGCAAGCCAAATGGTCTGTGGTAAAAAACAAAACAGACTTTGAGACTCAAGGCTAAAAAAACAGGGAAATGGCTGGCATTTGAGTCACACACTAACTGCATAGGACAAATGAATCTTGCTTAAACCAACTCATGCATTCTTGAAAAGGTATATGCAACCCAACTGTGTGTTAACTAAGCAATTTTTTTGCCATCTCACATTCTAACTCGAGAAAGATTCCATTTTCATTTTTCACCAACTGTTCTCTGAGCAGAGGTACCTGACTTTTGCACTGTGAGTGGTTTCTAATCTCAGTCTCTGTCAAGCAATGCTAAGAAAGCCAACACCTAAAGACACAAGGGGTACATCATTTAAATGAATAATGTAACCAAACAAACAAAAAAAGAGAATAATCATTAATAACTCAACTGATAGATATGTAGGGAGTAGGCAACCCAGGAAGTTTAAAACTAAATTCTGTTACTCTTGAGGGTTAACCAGCCCCTGGGAATGTTATGAGCAAATGATACTCCATGAGTAAAATGATATCTATGCAAGTAAAATAAATAATTTATCTAACTGGGAA (SEQ ID NO: 117) >NP_001235.1 tumor necrosis factor ligand superfamilymember 8 isoform 1 [Homo sapiens]MDPGLQQALNGMAPPGDTAMHVPAGSVASHLGTTSRSYFYLTTATLALCLVFTVATIMVLVVQRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKSWAYLQVAKHLNKTKLSWNKDGILHGVRYQDGNLVIQFPGLYFIICQLQFLVQCPNNSVDLKLELLINKHIKKQALVTVCESGMQTKHVYQNLSQFLLDYLQVNTTISVNVDTFQYIDTSTFPLENVLSIFLYSNSD (SEQ ID NO: 118) Mouse CD30L>NM_009403.3 Mus musculus tumor necrosis factor (CD153)(ligand) superfamily, member 8 (Tnfsf8), mRNAAGATTAATCCCAGGCGATGAAAAATGAACCTCTCCCCCACCCTTGCAGCCACCCTTCGCCTCACGCCCCCAGAGAAGAGTTTCTCCATCCGGCAACTGGTGAAGGCTTTTTTCCAAGTCACATGATCCAGGATGCAGGGGAAAATCCTTCTTGGAACAGAGCTGGGTACAGAACCGAATCAGATGAGGAGAGATAAGGTGTGATGTGGGACAGACTATATAAAGCATGGAGCCAGGGCTGCAACAAGCAGGCAGCTGTGGGGCTCCTTCCCCTGACCCAGCCATGCAGGTGCAGCCCGGCTCGGTAGCCAGCCCCTGGAGAAGCACGAGGCCCTGGAGAAGCACAAGTCGCAGCTACTTCTACCTCAGCACCACCGCACTGGTGTGCCTTGTTGTGGCAGTGGCGATCATTCTGGTACTGGTAGTCCAGAAAAAGGACTCCACTCCAAATACAACTGAGAAGGCCCCCCTTAAAGGAGGAAATTGCTCAGAGGATCTCTTCTGTACCCTGAAAAGTACTCCATCCAAGAAGTCATGGGCCTACCTCCAAGTGTCAAAGCATCTCAACAATACCAAACTGTCATGGAACGAAGATGGCACCATCCACGGACTCATATACCAGGACGGGAACCTGATAGTCCAATTCCCTGGCTTGTACTTCATCGTTTGCCAACTGCAGTTCCTCGTGCAGTGCTCAAATCATTCTGTGGACCTGACATTGCAGCTCCTCATCAATTCCAAGATCAAAAAGCAGACGTTGGTAACAGTGTGTGAGTCTGGAGTTCAGAGTAAGAACATCTACCAGAATCTCTCTCAGTTTTTGCTGCATTACTTACAGGTCAACTCTACCATATCAGTCAGGGTGGATAATTTCCAGTATGTGGATACAAACACTTTCCCTCTTGATAATGTGCTATCCGTCTTCTTATATAGTAGCTCAGACTGAATAGTTGTTCTTAACCTTTATGAAAATGCTGTCTACCATACAGTACTTCATCTGTCCAAACATGGGCCAAAGAAAATATTAGGACAACTCAAACTAAGCATGTGAGTTAGTGCACTTCTCTTTCTGTCCTTTGGAAAAATACAAACCCAGGATTTAGAAAGTGGAGTCTCCTTCAGATGCACAAACAGGAAAGAATGTGATATGTGCACAGAGACCTACTTGGGCACTAGAAGGGGTTGAGTTGTCCCAGTATAACCACTAATTCACTGACCTTGAGCCATTTTTCCTTCCCCTGGAACTTGGGGTCTGAATCTGGAAAAGTAGGAGATGAGATTTACATTTCCCCAATATTTTCTTCAACTCAGAAGACGAGACTGTGGAGCTGAGCTCCCTACACAGATGAAGGCCTCCCATGGCATGAGGAAAATGATGGTACCAGTAATGTCTGTCTGACTGTCATCTCAGCAAGTCCTAAGGACTTCCATGCTGCCTTGTTGAAAGATACTCTAACCTCTTGTAATGGGCAAAGTGATCCTGTCTCTCACTGAGGGGAGTAGCTGCTGCCATCTCCTGAGACATACATGGAGACATTTTCTGCCCAAATTCCATTCTGTGTGCAGTTTTTAAGTATTCCCCCAAAAGTTCTTGACAATGAGAACTTTGAATGTGGGAAGAGCTTCTGGACAGCAAACATTAACAGCTTCTCCTGACCAGAGAGACCATGCAAGCTTGGTCTTAGACCCATCAAGCTTGAGGTTTCTACATTGTGGGAGACAGACTTTTGACAAACCATTTGAGTTGATGTCTGGGCCCCTGGGAGTTCTCCTTCAGTAAGGAGAGCAAGCCGTTCTAGTGCTGTGTCAGAGGATGGAGTAAAATAGACACTTTTCTGAAGGAAAGGAGAACAAAGTTCCAGAAAAAGGCTAGAAAATGTTTAAAAGGAAAAGAAAAAACTCAGCTTTTCTCATATGAGAGGAACCCAGAAAAACAACACTGAAAAAGAAGAGTGGCTCTGTCAACCTCCTCTTAGGTCTCCTCCTCTCTAGTTATTGGGAAAGGAGTTGCATGGTACAGGACAAGTTCTGGTGTGTGGTCAAATAGAATCAGATGTGGAGAACACCATGCAGAGAATAAGGAGACCTGTCATATTTGTGTTGTACTCAAATGAGGGGCAAATGAATCTTAGGCTAAATCAAATAACAGTCTCTGTCAAGCTGTGCTCAGAAAGTCAACCACTGAAGATGGAGGGTGAGGCACGTCATTTAAAAAAAGTGAAATGTAGC (SEQ ID NO: 119) >NP_033429.1 tumor necrosis factor ligand superfamilymember 8 [Mus musculus]MEPGLQQAGSCGAPSPDPAMQVQPGSVASPWRSTRPWRSTSRSYFYLSTTALVCLVVAVAIILVLVVQKKDSTPNTTEKAPLKGGNCSEDLFCTLKSTPSKKSWAYLQVSKHLNNTKLSWNEDGTIHGLIYQDGNLIVQFPGLYFIVCQLQFLVQCSNHSVDLTLQLLINSKIKKQTLVTVCESGVQSKNIYQNLSQFLLHYLQVNSTISVRVDNFQYVDTNTFPLDNVLSVFLYSSSD (SEQ ID NO: 120) Human>NM_005092.4 Homo sapiens TNF superfamily member 18 GITRL(TNFSF18), mRNA ATCACTTGTGAATTTTTGTTTTCCACAGCTCTCATTTCTCCAAAAATGTGTTTGAGCCACTTGGAAAATATGCCTTTAAGCCATTCAAGAACTCAAGGAGCTCAGAGATCATCCTGGAAGCTGTGGCTCTTTTGCTCAATAGTTATGTTGCTATTTCTTTGCTCCTTCAGTTGGCTAATCTTTATTTTTCTCCAATTAGAGACTGCTAAGGAGCCCTGTATGGCTAAGTTTGGACCATTACCCTCAAAATGGCAAATGGCATCTTCTGAACCTCCTTGCGTGAATAAGGTGTCTGACTGGAAGCTGGAGATACTTCAGAATGGCTTATATTTAATTTATGGCCAAGTGGCTCCCAATGCAAACTACAATGATGTAGCTCCTTTTGAGGTGCGGCTGTATAAAAACAAAGACATGATACAAACTCTAACAAACAAATCTAAAATCCAAAATGTAGGAGGGACTTATGAATTGCATGTTGGGGACACCATAGACTTGATATTCAACTCTGAGCATCAGGTTCTAAAAAATAATACATACTGGGGTATCATTTTACTAGCAAATCCCCAATTCATCTCCTAGAGACTTGATTTGATCTCCTCATTCCCTTCAGCACATGTAGAGGTGCCAGTGGGTGGATTGGAGGGAGAAGATATTCAATTTCTAGAGTTTGTCTGTCTACAAAAATCAACACAAACAGAACTCCTCTGCACGTGAATTTTCATCTATCATGCCTATCTGAAAGAGACTCAGGGGAAGAGCCAAAGACTTTTGGTTGGATCTGCAGAGATACTTCATTAATCCATGATAAAACAAATATGGATGACAGAGGACATGTGCTTTTCAAAGAATCTTTATCTAATTCTTGAATTCATGAGTGGAAAAATGGAGTTCTATTCCCATGGAAGATTTACCTGGTATGCAAAAAGGATCTGGGGCAGTAGCCTGGCTTTGTTCTCATATTCTTGGGCTGCTGTAATTCATTCTTCTCATACTCCCATCTTCTGAGACCCTCCCAATAAAAAGTAGACTGATAGGATGGCCACAGATATGCCTACCATACCCTACTTTAGATATGGTGGTGTTAGAAGATAAAGAACAATCTGAGAACTATTGGAATAGAGGTACAAGTGGCATAAAATGGAATGTACGCTATCTGGAAATTTCTCTTGGTTTTATCTTCCTCAGGATGCAGGGTGCTTTAAAAAGCCTTATCAAAGGAGTCATTCCGAACCCTCACGTAGAGCTTTGTGAGACCTTACTGTTGGTGTGTGTGTCTAAACATTGCTAATTGTAAAGAAAGAGTAACCATTAGTAATCATTAGGTTTAACCCCAGAATGGTATTATCATTACTGGATTATGTCATGTAATGATTTAGTATTTTTAGCTAGCTTTCCACAGTTTGCAAAGTGCTTTCGTAAAACAGTTAGCAATTCTATGAAGTTAATTGGGCAGGCATTTGGGGGAAAATTTTAGTGATGAGAATGTGATAGCATAGCATAGCCAACTTTCCTCAACTCATAGGACAAGTGACTACAAGAGGCAATGGGTAGTCCCCTGCATTGCACTGTCTCAGCTTTAGAATTGTTATTTCTGCTATCGTGTTATAAGACTCTAAAACTTAGCGAATTCACTTTTCAGGAAGCATATTCCCCTTTAGCCCAAGGTGAGCAGAGTGAAGCTACAACAGATCTTTCCTTTACCAGCACACTTTTTTTTTTTTTCCTGCCTGAATCAGGGAGATCCAGGATGCTGTTCAGGCCTTATCCCAACCAAATTCCCCTCTTCACTTTGCAGGGCCCATCTTAGTCAAATGTGCTAACTTCTAAAATAATAAATAGCACTAATTCAAAATTTTTGGACTCTTAAATTAGCTACTTGCAGGTTCTTGTTGAAAGGTATATAATATTACATTGTAAACAAATTTAAAATATTTATGGATATTTGTGAAAAGCTGCATTATGTTAAATAATATTACATGTAAAGCTATTTAAAAGAGGTTTTTTTTGTATTTTGTTTAACAAAAATTGCTCAGGAGCATGCTAAGCCTGAGGCCAAGTTGTTTCTTAGTATGACTTTTTAAAAAAACATCTGCTGAGTAGCTACAGGGCCAAAGACTTGGAGAGCTTGTTTCTGTTGCATTTGCATATCTTCTCAGGAAATTAAAGTGTGTCATACATATGTGTGTGTGTGTGTGTGTGTGTGTGTATATGTGTGTGTGTATATATATGTATACTTATAAAATCTTGGTGTTCTTGATCTTTGTTGTGTTATAAGCAATGTGTGCTGGAGTGGGCTGGTGCTAGCTTATAAGCACATATTATTAAATTTTCAGGAATGTTGCACTTTAGTTATTAACTATAGGCATTCTTGAAATTGGCTATGGTGGGAGTATTTATACCATGTAAATTGGCAAACACTACACATTTTCCTTTTGGACAGCTAGTTCACCAGCACACCACTGTGAAACTCTCCTTAATGACTCCTCTCTGCCCCCGCTTCATTCCTGGGATAATCATAGCAGACTAAGGGAGAAAATGAAATTGTAAAAATTTGGCATACTGGTGATTTCTCAGGGCAAGCAGAGGTTACTACAGCTGCAGCTAGAGGGATGACTACCAACAGGTGACCTTTACATTTTCCTGATGTTATAATTTTAGCTTTTGTTTTCAATGTATACTGTTTTCCTGTTTCTCCACATAGTAGTCTGCATTTTAAATCTATAATAAAACATGCTGATAACTGG (SEQ ID NO:121) >NP_005083.3 tumor necrosis factor ligand superfamilymember 18 [Homo sapiens]MCLSHLENMPLSHSRTQGAQRSSWKLWLFCSIVMLLFLCSFSWLIFIFLQLETAKEPCMAKFGPLPSKWQMASSEPPCVNKVSDWKLEILQNGLYLIYGQVAPNANYNDVAPFEVRLYKNKDMIQTLTNKSKIQNVGGTYELHVGDTIDLIFNSEHQVLKNNTYWGIILLANPQFIS (SEQ ID NO: 122) Mouse GITRL>NM_183391.3 Mus musculus tumor necrosis factor(ligand) superfamily, member 18 (Tnfsf18), mRNATTGTGGGTATCTGCTTTCCCCAGTTCTCATTCCATCAGAGAACGAGTTCTAGCCTCATGGAGGAAATGCCTTTGAGAGAATCAAGTCCTCAAAGGGCAGAGAGGTGCAAGAAGTCATGGCTCTTGTGCATAGTGGCTCTGTTACTGATGTTGCTCTGTTCTTTGGGTACACTGATCTATACTTCACTCAAGCCAACTGCCATCGAGTCCTGCATGGTTAAGTTTGAACTATCATCCTCAAAATGGCACATGACATCTCCCAAACCTCACTGTGTGAATACGACATCTGATGGGAAGCTGAAGATACTGCAGAGTGGCACATATTTAATCTACGGCCAAGTGATTCCTGTGGATAAGAAATACATAAAAGACAATGCCCCCTTCGTAGTACAGATATATAAAAAGAATGATGTCCTACAAACTCTAATGAATGATTTTCAAATCTTGCCTATAGGAGGGGTTTATGAACTGCATGCTGGAGATAACATATATCTGAAGTTCAACTCTAAAGACCATATTCAGAAAACTAACACATACTGGGGGATCATCTTAATGCCTGATCTACCATTCATCTCTTAGAGATTGGGTTTGGTCTCCTCATCTTCTTCTTTGTATCCCGAGATGCTGGTGGGTGGGTTGGAGGGGGATGATTGATGGCAATGCACACAGTTTGTGAGGGCTTACAAATTGACACAATCAGAGCCTCTTGGCATATAAAATTTTAGCCCTCATATCTGTCTGAAGAGGACTCAGCAAATGGGCCAATCCCTAATGTTGGGTCTGCAAATGGACTTGTACAATCCATGATAAAAAGGAGTATGGGCCACAGAAGACAGAAACTCTTCCAAAGAATGTCTTTCTAACCTTGATCCCTGGGTAGAATGAGATCCTGTTTCCATGGGAGTCTTACTTGGCTTGCAAAAAAGGGTGTAGGGCAGTAGCTTGGCCTTTTTTCCATCATAATTTCCTTGAGCTGTTTTACCTTAATCCCTCCAAACTCTCACCTTCTGAGAGCCTCCTAATGAAACATTGTTAGACTGGTGGGGTGGCCAAGACATGCCAACAACACCCTTCTTTAGAGGTGGTGTTTTTAGAGGACAGAGAACATTATGAAGCCTAGAGCAGCAGAGGTCAAGATGCCACGAAATGGAATTGATCTGGGAATTTTTTTTTTTTTTCATTCTCAGGATGCAGGTTCATTCTGAACTTTCCCCTAGGCCTTCATTGCTTTTGTGTGTATGTGTGCATAAATTCTGCAAATAGAAAAATGAGAGTTTGCACCAGTACTCACTAGATTTAACACCAGAAAGTGGTACTTTTCTGGCTGTATTATGCCATGATAGCACATTTTCTGTTGGTGTTCCCTAACTGACAAGTATAACAGTTTTCCTAAACCACACAACAATGCTATGATGTTAATGGGGTAGATATTTTTGGAAAAAAATTGCACAGTGAGAACATGGGTAGATGAACCCTAAGACTCTTACCTCAATTCAGAACTCGCAAGGAGTTAAGTGAGTGGGGTCTTCATTAGACCATTCACATGGTCTCTGCTTTGAAACTGGCGTTGCTACTGTCTCATTATACATCACTAAAATGGAATTAACTCAACTTTGAAATGGATGCATCGACTTTACCCCAAGGTGTCCAGAATGAAGCTACAAGACTTTTACCAGCAGTCATTTTCCTTTTGCCTGGAGCAAGAAGATCCAGGATACTGTTGGAAGAGTTCATCTCACTCAACCATGCTGACTTTCCAAAGTAATAATGAACATTTGTGTTCAAATTTTGGATTCTGTTAAATTTAGCCAGCTTGTGAGTTCTTGTCGAAAAGTATTTTAAACCAATTTACACTATTTATGGGTATTTGTGAAAAGCTATATAGTGATATTTTATATATAACTAATTTAAAATATTTTTATTTTATGTAACAAAAATACTATAGGCTAAGCTATTTCTTCTTATTTTTTTATGAATACTTGCTGAATTGCCATAGGGCACAAAGACTCTTCTGTTTGCATATCTTCTCAGGAAATTAAAATTGTATCACATGTATTTATAAGAA(SEQ ID NO: 123) >NP_899247.3 tumor necrosis factor ligand superfamilymember 18 [Mus musculus]MEEMPLRESSPQRAERCKKSWLLCIVALLLMLLCSLGTLIYTSLKPTAIESCMVKFELSSSKWHMTSPKPHCVNTTSDGKLKILQSGTYLIYGQVIPVDKKYIKDNAPFVVQIYKKNDVLQTLMNDFQILPIGGVYELHAGDNIYLKFNSKDHIQKTNTYWGIILMPDLPFIS (SEQ ID NO: 124) Human>NM_000074.3 Homo sapiens CD40 ligand (CD40LG), mRNA CD40LAATCCTGAGTAAGGTGGCCACTTTGACAGTCTTCTCATGCTGCCTCTGCCACC (CD154)TTCTCTGCCAGAAGATACCATTTCAACTTTAACACAGCATGATCGAAACATACAACCAAACTTCTCCCCGATCTGCGGCCACTGGACTGCCCATCAGCATGAAAATTTTTATGTATTTACTTACTGTTTTTCTTATCACCCAGATGATTGGGTCAGCACTTTTTGCTGTGTATCTTCATAGAAGGTTGGACAAGATAGAAGATGAAAGGAATCTTCATGAAGATTTTGTATTCATGAAAACGATACAGAGATGCAACACAGGAGAAAGATCCTTATCCTTACTGAACTGTGAGGAGATTAAAAGCCAGTTTGAAGGCTTTGTGAAGGATATAATGTTAAACAAAGAGGAGACGAAGAAAGAAAACAGCTTTGAAATGCAAAAAGGTGATCAGAATCCTCAAATTGCGGCACATGTCATAAGTGAGGCCAGCAGTAAAACAACATCTGTGTTACAGTGGGCTGAAAAAGGATACTACACCATGAGCAACAACTTGGTAACCCTGGAAAATGGGAAACAGCTGACCGTTAAAAGACAAGGACTCTATTATATCTATGCCCAAGTCACCTTCTGTTCCAATCGGGAAGCTTCGAGTCAAGCTCCATTTATAGCCAGCCTCTGCCTAAAGTCCCCCGGTAGATTCGAGAGAATCTTACTCAGAGCTGCAAATACCCACAGTTCCGCCAAACCTTGCGGGCAACAATCCATTCACTTGGGAGGAGTATTTGAATTGCAACCAGGTGCTTCGGTGTTTGTCAATGTGACTGATCCAAGCCAAGTGAGCCATGGCACTGGCTTCACGTCCTTTGGCTTACTCAAACTCTGAACAGTGTCACCTTGCAGGCTGTGGTGGAGCTGACGCTGGGAGTCTTCATAATACAGCACAGCGGTTAAGCCCACCCCCTGTTAACTGCCTATTTATAACCCTAGGATCCTCCTTATGGAGAACTATTTATTATACACTCCAAGGCATGTAGAACTGTAATAAGTGAATTACAGGTCACATGAAACCAAAACGGGCCCTGCTCCATAAGAGCTTATATATCTGAAGCAGCAACCCCACTGATGCAGACATCCAGAGAGTCCTATGAAAAGACAAGGCCATTATGCACAGGTTGAATTCTGAGTAAACAGCAGATAACTTGCCAAGTTCAGTTTTGTTTCTTTGCGTGCAGTGTCTTTCCATGGATAATGCATTTGATTTATCAGTGAAGATGCAGAAGGGAAATGGGGAGCCTCAGCTCACATTCAGTTATGGTTGACTCTGGGTTCCTATGGCCTTGTTGGAGGGGGCCAGGCTCTAGAACGTCTAACACAGTGGAGAACCGAAACCCCCCCCCCCCCCCCGCCACCCTCTCGGACAGTTATTCATTCTCTTTCAATCTCTCTCTCTCCATCTCTCTCTTTCAGTCTCTCTCTCTCAACCTCTTTCTTCCAATCTCTCTTTCTCAATCTCTCTGTTTCCCTTTGTCAGTCTCTTCCCTCCCCCAGTCTCTCTTCTCAATCCCCCTTTCTAACACACACACACACACACACACACACACACACACACACACACACACACACACAGAGTCAGGCCGTTGCTAGTCAGTTCTCTTCTTTCCACCCTGTCCCTATCTCTACCACTATAGATGAGGGTGAGGAGTAGGGAGTGCAGCCCTGAGCCTGCCCACTCCTCATTACGAAATGACTGTATTTAAAGGAAATCTATTGTATCTACCTGCAGTCTCCATTGTTTCCAGAGTGAACTTGTAATTATCTTGTTATTTATTTTTTGAATAATAAAGACCTCTTAACATTA (SEQ ID NO: 125)>NP_000065.1 C040 ligand [Homo sapiens]MIETYNQTSPRSAATGLPISMKIFMYLLTVFLITQMIGSALFAVYLHRRLDKIEDERNLHEDFVFMKTIQRCNTGERSLSLLNCEEIKSQFEGFVKDIMLNKEETKKENSFEMQKGDQNPQIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLENGKQLTVKRQGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGRFERILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFTSFGLLKL (SEQ ID NO: 126)Mouse CD40L >NM_011616.2 Mus musculus CD40 ligand (Cd40lg), mRNACTTTCAGTCAGCATGATAGAAACATACAGCCAACCTTCCCCCAGATCCGTGGCAACTGGACTTCCAGCGAGCATGAAGATTTTTATGTATTTACTTACTGTTTTCCTTATCACCCAAATGATTGGATCTGTGCTTTTTGCTGTGTATCTTCATAGAAGATTGGATAAGGTCGAAGAGGAAGTAAACCTTCATGAAGATTTTGTATTCATAAAAAAGCTAAAGAGATGCAACAAAGGAGAAGGATCTTTATCCTTGCTGAACTGTGAGGAGATGAGAAGGCAATTTGAAGACCTTGTCAAGGATATAACGTTAAACAAAGAAGAGAAAAAAGAAAACAGCTTTGAAATGCAAAGAGGTGATGAGGATCCTCAAATTGCAGCACACGTTGTAAGCGAAGCCAACAGTAATGCAGCATCCGTTCTACAGTGGGCCAAGAAAGGATATTATACCATGAAAAGCAACTTGGTAATGCTTGAAAATGGGAAACAGCTGACGGTTAAAAGAGAAGGACTCTATTATGTCTACACTCAAGTCACCTTCTGCTCTAATCGGGAGCCTTCGAGTCAACGCCCATTCATCGTCGGCCTCTGGCTGAAGCCCAGCAGTGGATCTGAGAGAATCTTACTCAAGGCGGCAAATACCCACAGTTCCTCCCAGCTTTGCGAGCAGCAGTCTGTTCACTTGGGCGGAGTGTTTGAATTACAAGCTGGTGCTTCTGTGTTTGTCAACGTGACTGAAGCAAGCCAAGTGATCCACAGAGTTGGCTTCTCATCTTTTGGCTTACTCAAACTCTGAACAGTGCGCTGTCCTAGGCTGCAGCAGGGCTGATGCTGGCAGTCTTCCCTATACAGCAAGTCAGTTAGGACCTGCCCTGTGTTGAACTGCCTATTTATAACCCTAGGATCCTCCTCATGGAGAACTATTTATTATGTACCCCCAAGGCACATAGAGCTGGAATAAGAGAATTACAGGGCAGGCAAAAATCCCAAGGGACCCTGCTCCCTAAGAACTTACAATCTGAAACAGCAACCCCACTGATTCAGACAACCAGAAAAGACAAAGCCATAATACACAGATGACAGAGCTCTGATGAAACAACAGATAACTAATGAGCACAGTTTTGTTGTTTTATGGGTGTGTCGTTCAATGGACAGTGTACTTGACTTACCAGGGAAGATGCAGAAGGGCAACTGTGAGCCTCAGCTCACAATCTGTTATGGTTGACCTGGGCTCCCTGCGGCCCTAGTAGG (SEQ ID NO: 127)>NP_035746.2 CD40 ligand [Mus musculus]MIETYSQPSPRSVATGLPASMKIFMYLLTVFLITQMIGSVLFAVYLHRRLDKVEEEVNLHEDFVFIKKLKRCNKGEGSLSLLNCEEMRRQFEDLVKDITLNKEEKKENSFEMQRGDEDPQIAAHVVSEANSNAASVLQWAKKGYYTMKSNLVMLENGKQLTVKREGLYYVYTQVTFCSNREPSSQRPFIVGLWLKPSSGSERILLKAANTHSSSQLCEQQSVHLGGVFELQAGASVFVNVTEASQVIHRVGFSSFGLLKL (SEQ ID NO: 128) Human>NM_003807.5 Homo sapiens TNF superfamily member 14 LIGHT(TNFSF14), transcript variant 1, mRNA (CD258)CGAGACTCCATCTCAAAAACAAAACAAATAAACGAACAAAAAAACCCACAACGTATTATTTTCTTGTTTACGAGGTTTCTTGTCTCTCTGGCTCCACCAGAAGAGGAGCAGGGACCCTTCTTGCTGTTGTTCATTGCTGCATCCCCCACACCGAGAGCAGAGCCTGGCATGGGCAGAAAGTCCTCAGTCGATATTTGGTGGCCCCAAGCGAATGAAGCATCCAAGAAGGGAAAGCTGGGGGCTCCCCACTGCACTTGCCACCTGAGTCACATTTTCAGAAGCCTCTGGAAAGTCGTGCACAGCCCAGGAGTGTTGAGCAATTTCGGTTTCCTCTGAGGTTGAAGGACCCAGGCGTGTCAGCCCTGCTCCAGACACCTTGGGCATGGAGGAGAGTGTCGTACGGCCCTCAGTGTTTGTGGTGGATGGACAGACCGACATCCCATTCACGAGGCTGGGACGAAGCCACCGGAGACAGTCGTGCAGTGTGGCCCGGGTGGGTCTGGGTCTCTTGCTGTTGCTGATGGGGGCCGGGCTGGCCGTCCAAGGCTGGTTCCTCCTGCAGCTGCACTGGCGTCTAGGAGAGATGGTCACCCGCCTGCCTGACGGACCTGCAGGCTCCTGGGAGCAGCTGATACAAGAGCGAAGGTCTCACGAGGTCAACCCAGCAGCGCATCTCACAGGGGCCAACTCCAGCTTGACCGGCAGCGGGGGGCCGCTGTTATGGGAGACTCAGCTGGGCCTGGCCTTCCTGAGGGGCCTCAGCTACCACGATGGGGCCCTTGTGGTCACCAAAGCTGGCTACTACTACATCTACTCCAAGGTGCAGCTGGGCGGTGTGGGCTGCCCGCTGGGCCTGGCCAGCACCATCACCCACGGCCTCTACAAGCGCACACCCCGCTACCCCGAGGAGCTGGAGCTGTTGGTCAGCCAGCAGTCACCCTGCGGACGGGCCACCAGCAGCTCCCGGGTCTGGTGGGACAGCAGCTTCCTGGGTGGTGTGGTACACCTGGAGGCTGGGGAGAAGGTGGTCGTCCGTGTGCTGGATGAACGCCTGGTTCGACTGCGTGATGGTACCCGGTCTTACTTCGGGGCTTTCATGGTGTGAAGGAAGGAGCGTGGTGCATTGGACATGGGTCTGACACGTGGAGAACTCAGAGGGTGCCTCAGGGGAAAGAAAACTCACGAAGCAGAGGCTGGGCGTGGTGGCTCTCGCCTGTAATCCCAGCACTTTGGGAGGCCAAGGCAGGCGGATCACCTGAGGTCAGGAGTTCGAGACCAGCCTGGCTAACATGGCAAAACCCCATCTCTACTAAAAATACAAAAATTAGCCGGACGTGGTGGTGCCTGCCTGTAATCCAGCTACTCAGGAGGCTGAGGCAGGATAATTTTGCTTAAACCCGGGAGGCGGAGGTTGCAGTGAGCCGAGATCACACCACTGCACTCCAACCTGGGAAACGCAGTGAGACTGTGCCTCAAAAAAAAGAAAGGAAGAAAAAAGAAAACTCAGGAAACAGATCTTGGGGGACACTCCAGGGAACCCAAAACTCAAAGGCGGAGAGCTCAGTGGGCACCACCAAGGCGAGATGAAGCCCCAGCAGGCACCTTCAGAAGACCCACGTAGACTGCAGACCCTGCCACGGACAATACTAAGGACAAAAACCCAGAGACTTGGGGTCTGTGGGCCCCCAAACATGGGGTAAAGTTGATTTGCCTGATATTCAGGAAGAAGGGGTGAGGGGTGGGTATTTATGCTTTTGATTCAGAAGAAAGTGGGGCTTGGGATTCCAGGGACTTGGCTGGGGGTGGGAAACTTCATCCACTTCCCTACTCTCATCATGAGTACGGACAGGGTGGGCGGGAGACTGATCATCGGGACTCATCATGAAGAGCCCAGCCCCACCCCACATACTCAGATCCCACCCACAGACTGGTGGCCACACCTCAGCCTGGTCACAAAGAGTTACACTCAGATACATGAGCACGGCAGCGTGCTCATAACTGTTTAACAACCAGCTGTCCTGGGAGGGGGACAGCTTTGTAATGTTTGCCAATTTCCATGGTGTAAATGCTACCACCATGGCTGATTTCATCACTGCCAAGCATAGACATCCCTAATAGGACACCACGGATCTGTCCCCGGCATCCGGCCCAGGGCCTGGCACAAAGCATGCTCTAGGGAAATGCTTGCTGATTGAAAGGAAGGAAGAATGACTCTACAGTCACACCTATGGCATCCCACAAAATCTGTCACATGGCTGCATAATCTCAGCCACTCTTTCACAACTATAGACTCATACACGCGAAGTGCCAGATTCATGCACAACCACACAATCACATGGAAGTCACAGACGGCATCACAGACAGTCACAGCACTGTGTGTATGTTATAACACAAGCACACAAAACTCAGACAGCATCCCAGCTACACAGCCACTCCCAGAGGTGTCACCGTCACACTTGGTAATTAATACTCATTACATTAGACACAGACAGACCAAGTTATAGTCAGACCTGGTTACACACATACACACACACAATATCACCATGACAAATACACATTACACACACACAACATCACAATGACAAACACACATTACACACACAACATCACGATGACAAACACACATTACACACACAACATCACGATGACAAACACACATTACACACACATCACAATGACAAACACAACATTACACACACACAACATCACAATGACACACACATCACACACACATCACAATGACAAACACACAACATTACACACATATACACACAGCCTGAGGGCCCTCCCCAGCCCAGACTAACACATCTCGGGGTGAGGACCAGACCTTGTTCATAACCCTGGGCCTCTTAACCACTGATCTTTGAAATAAATGGCAAATAGTTGTACCTGGATCTGTCTAGTTCTTAGGGGAACAAACTGAAGAAGGGTGGAGAGGAATTGTCAGGCCTAAAGAGCCCCACAGGGAAAGGGAGGAGTCGGATGGGGGGCAACCATCAGCAACAAGTGGTGGCTCCTAGAGGCAGAGGGATGGAGGTAATGACCCATGGAGGTCATTCTACAGATGAGGAACCTGGACCCAGTTGGCTCAAGTCCATGCAGGAAATGTGGGGGAAACCAGAGACCTCACGTCTGGATCTGGCTTCCTCTCCAATCCACAATTCCTGAGGAAGTAGAGGCTACATCCCGCAAGACGCCCTTATTAGACACATCCAGGACAGAATGACAATCCGCCAAGCCAGCTGGAAGCATAAAACACAGGGAGCTGGTGGGTTGGGTGGGGGCAGATAATGATATGCATACAAATTAGAGGGTCTATGCAAATGAGCATTGCTGCAGTGTGGCTGGAGGGAATCCTTAGTTCCTAGGATTCTAGGATATGGGTTTCGACCCCAGAGGTGAATGTATTGTTATTATTGTTTTGTTGTTGTTGTGAATGACAAGTCAAAATTTGTGGGTTATTGTTGTTATCGCCAATAGTATTCTTGTCATTGTTGCACAGTACAGAGATGAAGGAAACAGATTTTGCAATCAGATGATCCTGGGTTCTGAGTCCACTCTGCCACTCACCAGCTATATGACCTCCAGCAATTTCCATCACCTCTCAATGCTTCAGTTTCCCCATCGGCAAGATGGTTGTGGGGGGAGAGGAACAACAGTACAGATTCACCATCCCAAATTCAAAATGCTCCAAAATCTAGGCCGGGCGTGGTGGCTCATACCTGTAATCCCAGCACTTTGGGAGGTCAAAGTGGACGGATAACCTGAGGTCAGGAGCTCCAGACCAGCCTGGCCAACATGGCGAAACCCCATCTCTACTAAAAATACAAAAAATTACCTGGGTGTGGTGGGGGGCACCTGTAACCCCAGCTACTCGGGAGGCTGAGGCAGGAACCCTGGAGGTTGAGGTTGCAGTGAGCTGAGATCACACCACTGCACTCCAGCCTGGGTGACAGAGCAAGGCTCCCATCTCAAAAAACAAAAAAACATGCTCCAAAATCTGAAACTCTTTGAGCCCCAGTGTGATGCCACAAGTGGGAAATTCCACAACTCATCACATGTGATAGATTGCAGTGGAAATGCAGGCACACACCACGAAGTTTACTCAGCATCCTCAAAGGAAATCCCCGTCAGTAGCTATATATCATTTTCTCACATGCCAGATAGGTATCTCTCATCTTTTACTGTTAGGTACTTCTGTGTTGAATAGGTGGAGGAAAATGATTGCTGGTTAGTAGTATATAAATTCAGAGTCAGGAAGGATGGTGATGTCGGCTGGGTGCAGTGGCTCATGCCTGTAATTCCAATGTGATACCCTACCTTGTGTTTAACGTGATTGACTCTCCCTTAGCTGAGAGGGCCAGGCAGACTCTATTTTGGCTTCTTCGCTTGCAGTCTCTCACCCACCCCCCTTCCTCAAGGACTTAAGCTGACTCCCAGCACATCCAAGAATGCGATTACTGATAAGATACTGTGACAAGCTATATCCACAATTCCCAGGAATTCGTCCGGTTGATAGCACCCAAAGCCCCCGCGTCTATCACCTTGTGATAGATTTAAAGCCCCTGCACCTGGAACTGTTTGTTTTTCTGTTACCATTTATCTTTTTCACTTTCTTGCCTGTTTTGCTTCTGTAAAATTGCTTCAGCTCGGCTCCCTCTTCCCCTTCTAAACCAAGGTATAAAAAGAAACCTAGCCCCTTCTTTGGGGTGGAGAGAATTTTGAGCGCTAGCCGTCTCTCAGTCGCCGGCTAATAAAGGACTCCTGAATTAGTCTAA (SEQ ID NO: 129) >NP_003798.2 tumor necrosis factor ligand superfamilymember 14 isoform 1 [Homo sapiens]MEESVVRPSVFVVDGQTDIPFTRLGRSHRRQSCSVARVGLGLLLLLMGAGLAVQGWFLLQLHWRLGEMVTRLPDGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGSGGPLLWETQLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGLASTITHGLYKRTPRYPEELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHLEAGEKVVVRVLDERLVRLRDGTRSYFGAFMV (SEQ ID NO: 130) Mouse LIGHT>NM_019418.3 Mus musculus tumor necrosis factor(ligand) superfamily, member 14 (Tnfsf14), mRNATTTTGCAGTTTGCACAGCCCGAGCGTGTTGGGCAATTGTGGTTTCCTCCGGAGAGGAGGAACTCAGGCTTGCCAACCCTTTCCCTGGGCTTCGGAGCCTCAGCTGCTCTGGCATGGAGAGTGTGGTACAGCCTTCAGTGTTTGTGGTGGATGGACAGACGGACATCCCATTCAGGCGGCTGGAACAGAACCACCGGAGACGGCGCTGTGGCACTGTCCAGGTCAGCCTGGCCCTGGTGCTGCTGCTAGGTGCTGGGCTGGCCACTCAGGGCTGGTTTCTCCTGAGACTGCATCAACGTCTTGGAGACATAGTAGCTCATCTGCCAGATGGAGGCAAAGGCTCCTGGGAGAAGCTGATACAAGATCAACGATCTCACCAGGCCAACCCAGCAGCACATCTTACAGGAGCCAACGCCAGCTTGATAGGTATTGGTGGACCTCTGTTATGGGAGACACGACTTGGCCTGGCCTTCTTGAGGGGCTTGACGTATCATGATGGGGCCCTGGTGACCATGGAGCCCGGTTACTACTATGTGTACTCCAAAGTGCAGCTGAGCGGCGTGGGCTGCCCCCAGGGGCTGGCCAATGGCCTCCCCATCACCCATGGACTATACAAGCGCACATCCCGCTACCCGAAGGAGTTAGAACTGCTGGTCAGTCGGCGGTCACCCTGTGGCCGGGCCAACAGCTCCCGAGTCTGGTGGGACAGCAGCTTCCTGGGCGGCGTGGTACATCTGGAGGCTGGGGAAGAGGTGGTGGTCCGCGTGCCTGGAAACCGCCTGGTCAGACCACGTGACGGCACCAGGTCCTATTTCGGAGCTTTCATGGTCTGAAGGCTGCGGTGACAATGTATTTTGTGGAGGGACCTCTCCAGGACTCACCTCAAACCCAGCAATAGGGTTTGAAGTCCTCCCTTTAAGGAGCCCTGAACTCTGCAGTGCTCGGGGCGGTGTAGACTGOTGACCTGCTTTGGGCAATCTTCAAATCAGAGACCTGGAGACTTGGGGCGTGGAGCCCAGGAGCGAGGGGTCAGCTCATTTGCCTGATATTCAGGAAGAAAGAATCAAGCTGGGGTATTTATGCTTCTGATGCAAACACTGAGATTTCGGCTTTCTGGGTTTTGAGCTGGAGGCAAGAAACCTTCCCAGAGTGTCATCAGGACCATGTTGGCAGGACTTGGGGCTCCAGACTTGCCACCACACTCTGGCCTCTCCCATCCATCCGCTGCATTGGTTTCCAGCCACCAAAACAGCACTGGCCCCCTGGCTGCAACTGGCCAGGTACGAGCTTCTGAGCACCTACATTCCTCAGGGACATCTTGATGAGATCTCAGTACTCAGTCCAATGCGCAGCAGCGACAGACATGCCAGGAATGGTTGGTCAGAAGGGAAGGGAGGAAAGGGAGGAAAGAAGGGAATGCAGAAGAGAAGGGGGGAAAACAAGACCAAAACAAAACAGCAACAACAAAGCGGCAGGGAGGAGGTGACACCCTTGGGGATACTTTAGTCAACACACTTAGAACAGATTGTGCCAGGCCTGTTGGATTCCTGGAGTTGATGGGATCGTGGGAAGGCACAATGGGGAGCAAGTGGGCTTGGGTTATGGCTCAGTGGGTAAAGTGCAATTATGGGGATCTGAGTTTGAATCCCTGGTACCCATATAAAGACACAGATGCGGTGATGGGCACTTGTGACAATGAGATCATCAATAGGGAATGGAGACAGGAGGGACCTCTGGGGTTCACTGGCCAGGCAGTCTAGCTGAATCAAAGAGCTCCAAGTTCAGTCGATAGCTCCTGAAGATGACAACTGAGGCTATTCTCCAAACCCCACACGCAGGACACATGCGTAATAAATAAAATTTTAAAAAT (SEQ ID NO: 131) >NP_062291.1 tumor necrosis factor ligand superfamilymember 14 [Mus musculus]MESVVQPSVFVVDGQTDIPFRRLEQNHRRRRCGTVQVSLALVLLLGAGLATQGWFLLRLHQRLGDIVAHLPDGGKGSWEKLIQDQRSHQANPAAHLTGANASLIGIGGPLLWETRLGLAFLRGLTYHDGALVTMEPGYYYVYSKVQLSGVGCPQGLANGLPITHGLYKRTSRYPKELELLVSRRSPCGRANSSRVWWDSSFLGGVVHLEAGEEVVVRVPGNRLVRPRDGTRSYFGAFMV (SEQ ID NO: 132) Human TL1>NM_005118.4 Homo sapiens TNF superfamily member 15(TNFSF15), transcript variant 1, mRNAAGAGGTGCCTCCAGGAGCAGCAGGAGCATGGCCGAGGATCTGGGACTGAGCTTTGGGGAAACAGCCAGTGTGGAAATGCTGCCAGAGCACGGCAGCTGCAGGCCCAAGGCCAGGAGCAGCAGCGCACGCTGGGCTCTCACCTGCTGCCTGGTGTTGCTCCCCTTCCTTGCAGGACTCACCACATACCTGCTTGTCAGCCAGCTCCGGGCCCAGGGAGAGGCCTGTGTGCAGTTCCAGGCTCTAAAAGGACAGGAGTTTGCACCTTCACATCAGCAAGTTTATGCACCTCTTAGAGCAGACGGAGATAAGCCAAGGGCACACCTGACAGTTGTGAGACAAACTCCCACACAGCACTTTAAAAATCAGTTCCCAGCTCTGCACTGGGAACATGAACTAGGCCTGGCCTTCACCAAGAACCGAATGAACTATACCAACAAATTCCTGCTGATCCCAGAGTCGGGAGACTACTTCATTTACTCCCAGGTCACATTCCGTGGGATGACCTCTGAGTGCAGTGAAATCAGACAAGCAGGCCGACCAAACAAGCCAGACTCCATCACTGTGGTCATCACCAAGGTAACAGACAGCTACCCTGAGCCAACCCAGCTCCTCATGGGGACCAAGTCTGTATGCGAAGTAGGTAGCAACTGGTTCCAGCCCATCTACCTCGGAGCCATGTTCTCCTTGCAAGAAGGGGACAAGCTAATGGTGAACGTCAGTGACATCTCTTTGGTGGATTACACAAAAGAAGATAAAACCTTCTTTGGAGCCTTCTTACTATAGGAGGAGAGCAAATATCATTATATGAAAGTCCTCTGCCACCGAGTTCCTAATTTTCTTTGTTCAAATGTAATTATAACCAGGGGTTTTCTTGGGGCCGGGAGTAGGGGGCATTCCACAGGGACAACGGTTTAGCTATGAAATTTGGGGCCCAAAATTTCACACTTCATGTGCCTTACTGATGAGAGTACTAACTGGAAAAAGGCTGAAGAGAGCAAATATATTATTAAGATGGGTTGGAGGATTGGCGAGTTTCTAAATATTAAGACACTGATCACTAAATGAATGGATGATCTACTCGGGTCAGGATTGAAAGAGAAATATTTCAACACCTTCCTGCTATACAATGGTCACCAGTGGTCCAGTTATTGTTCAATTTGATCATAAATTTGCTTCAATTCAGGAGCTTTGAAGGAAGTCCAAGGAAAGCTCTAGAAAACAGTATAAACTTTCAGAGGCAAAATCCTTCACCAATTTTTCCACATACTTTCATGCCTTGCCTAAAAAAAATGAAAAGAGAGTTGGTATGTCTCATGAATGTTCACACAGAAGGAGTTGGTTTTCATGTCATCTACAGCATATGAGAAAAGCTACCTTTCTTTTGATTATGTACACAGATATCTAAATAAGGAAGTATGAGTTTCACATGTATATCAAAAATACAACAGTTGCTTGTATTCAGTAGAGTTTTCTTGCCCACCTATTTTGTGCTGGGTTCTACCTTAACCCAGAAGACACTATGAAAAACAAGACAGACTCCACTCAAAATTTATATGAACACCACTAGATACTTCCTGATCAAACATCAGTCAACATACTCTAAAGAATAACTCCAAGTCTTGGCCAGGCGCAGTGGCTCACACCTGTAATCCCAACACTTTGGGAGGCCAAGGTGGGTGGATCATCTAAGGCCGGGAGTTCAAGACCAGCCTGACCAACGTGGAGAAACCCCATCTCTACTAAAAATACAAAATTAGCCGGGCGTGGTAGCGCATGGCTGTAATCCTGGCTACTCAGGAGGCCGAGGCAGAAGAATTGCTTGAACTGGGGAGGCAGAGGTTGCGGTGAGCCCAGATCGCGCCATTGCACTCCAGCCTGGGTAACAAGAGCAAAACTCTGTCCAAAAAAAAAAAAATAAAATAATAACTCCAAGCCTTTAAAAAATATCATCTGAAACTGTTACATCAGATTTCTGGCACTCTACTGACTGTGGAAGATAGCCAGCTGACTGGAAGATAGCCAGCTGATTAGTTCCCTGAAGAAACCTGAAGACAGATACCTGGTTAACTAGATCAACTACACTGCCAACTTGTTTGATGCTGAGAGACAATGGACTTATTCCATGGGGGAAGGGAAAAAAGAAGTCAATCACCAAATCTGAAGAAGTTAACCTAGATCTTTGAGGTTTGATTTGCAACTTTATATGCAGAGTATTATGTGGGTATTTTCCCTTAAAATATTCAAAGGGATTTACATATGGGATTAGCTAATGAGCCTAGCCAAGACCTTCCCTGGAGGACAGGCTGGTCATTGCGGAGGTCCCTTCTGTGCTTCAGTGGGTTCATATCCTCTAGTCCGTATGATTTTCCTACGCTAATATGTCAAGGGCAGGAGAGGCAGCTCTGTTCTCCTAGCCTTTGTTGACTTGTCTGCAAAGCAGGAATCTGCCCATTTGTTTCCAAGGAGCAAATGAGCTCATGAGAATGAAAGATGTTAACTTCATGCATTCTGTGCCATCTGAGCATTTCGGTATTATATGACTGGTGACCCTTGGCCCGTATTATAAATGCTTCCTATCCTGGGAGACCTCATGGATGAGTCTGAGAGGAAATTTGGCACCAAAATCACTCTCACTCTGGTTTCCAGTAGACTATAGAGGCAGAGAGGCATTTGAGAGGCTCCTGAGCAAAGTGTCCAGTGTAGCAGGAGCACTTCATTAATATTTATTGAGTTATAATTAAATAAAAATTAATTTCTGATTTCTCAGTTTGGAGGTTAAGGCTCTAAATATATTTTCTAACCTCTGCTAGGCTAACTTAAGCCAGGCCTTTTTCTTGCCTTCCCTTTCTCAAAACAGTCAGCACAGACTCAGTGGGAGCACAGAGGAGTGTGGTCACCTCCACCTGGCTCACCAGAGTCTTCATAGAGGAAGTGAAGCCTGGAAGAAACTGGGCGGGCCCCAGATGACCACAGGGAAAGGGCATCTCAGATGGAGGAATTACCCTTGACTTAAAGCAGAAAAGAAAGATTTCTCAGTAACTCCAAAACTTGCTTGATAGGAGAATATTCCCTCAACCAATTCCTAGGACAATATTTATTGGTAGATCAAGAATGTTTCCTCAATAACTCTAGTCTAGCTCCATGATCAGAACTAACACCCATTAAAAACATAAAATGTTCTTTCTGAACCGGTCTTCATGGTGCGTGAGAGCACCAAGCAGCTTTGGTATGCAGGAGGAGTTTTGCACAGAAGAGTGGCCTGCTCAAACCTGCCCACTGTTCTGTAGGTGATCTGGTGGATCTGGAAATTTATCCCAAGACAGGAATTTCCTAATATTCGAAGACATTTGAGGCTTTGGGAAATTCTCTGCTGTGCATTTATTTGGCTCCTGTCATAAGCTTGTTTTTTAAAGAATGTATCATAGCTCAAGTTTTTACTGCTGATTTTGTTAAATTCTGTATAGTATATTTTTTACGGAAAGGCACAGTCAGACATTCCTAATAGGGCTCATGTCAGAACTTCTGTTCCCAAGGCATTATCTCCATAGCAAAAATTAGTGCACTGTTTTCAAAAGTGAGGTGGGAAAATGCTTTTAAGATCATGTGATGTTCCCCTAAAAGGGGTTAATGGGGTGTATTCAGGGTTTGGGAGGGAGGAAGAAGCATGCTTTAGAAAACAGTAAATTTAGGGAGAAAATGCTTTGTTGGTTAAATGTCACTCAAAAGGCTGAATTCAAATCAATTCCACAAACATTTACTGAGTACCTACTGCCCCTGGGGACACAGAGATAAATTATTTAGTCTCAGACACACTCATTCTAACTTCCCAGCACCTCTACTGTCTGCAGATTCTTTAATTTATTTTGGTTGTATTAGCTAATTAATTCGTAAACTTTAGGCACATGGATCTATTCTCATTATGAAAATGGATGCCATTTGATTAAGGCTGATGACTAACAAAATGATTTGTGTTTACTCGAAGTGTTTTTTTAAAAATAGCTACTCAAGGATAGTTTTCCATAAATCAAGAAGGTAAAAAAGTTCCCATTTTTTATTGTAGAATCCATTATTTAAACTACATGTAGAGACAGGTTATTATTTGCTATATTCAAGTTTGGTCATCAATACCCTTAAAAATATTAGAATTTTATGGATGACCCAGAAATGCTTTGAAAATCTGTGTTCCTCAGCAAATACAGAGACCATGATCAAAATGCACAGAATCACTAACATTTTGATGCTAGCATGGTTTCAGTCTATTTGGCAGAACAGAATTGATTATGCTACTAAAATTTCTTTTTCTTTTTTTTTTTTTTTTTTTTTGAGACAGAGTCTTGCTTTGTCACCCAGGCTGAAGTGCAGTGGCAGGATCTCAGTTCACTGCAACCTCTGCCTCCCAGGTTCACGCCATTCTCCTGCTTCAGCCTCCCGAGTAGCTGGGACTACAGGCTCCCACCACCATGCCCGGCTAATTTTTTGCATTTTTAGTAGAGACGGGGTTTCACCGTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCAGCCTTCCAAAGTGCTGGGATTACAGGCGTGAGCCACTGTGCCCGGACTCTGATTTTTTTTTTACTAAGGTACAGTAAGAAAAGGGAAAAGTGTACGTTTTCACTTCCTGAAATATGTCAGGTTGAATCAATAATAGAGCACACCAGAACTCTTGGCTCCATTTCAACCTAAACTATTCAGTTCTCATCACCCCAGAGGAAATTCCGCCTCTGTGCTGGTCAGTAATCCCCCTGGATTATAAAAGTTTAACTAACTCACTGTGCACAAGGCACGGCCATTGCCAACATTCTCTTGCAAGGTATTTTCCCAAGCCCTTACCCAATTCTGTTTCCATGATTGTGACATTGGGGATTAATTCTGCAAGACAGAACTGTTTATATTCTGTACCTTAAAAACACATGCAAACATCTCTTGCCTTAAGATTTCTGGCTTTCCTATGGCCCAGAGTCCTAGAAGTGTTTTGATATTTGTAGCAGAATTTTCAAGTGTACATCCTTATCCTGGATATTAACATTTTTGCATCATATTGGCAGCTGGACCTACAGAGAATTTAGTAGACTGTTAACCTAATAAGCCTTGAATCCTTTTGCACCAGTGGTGAGAGAATGTGGATCAGAGCCATCACCTCCATGCCCCGTCACCCTCTAACAACCACATTTACAACTTCCCCAGCTCTGAGACACACTTGCCTCCACCCCTTCCATCACCCCATTTTAAGATGAAAATACCACACCAGCCTGGAAGGAAGAAGTTACTTGCCCAGGGCCACATAGTGAGTTAAGGGCTGATCTAGAGCTAGGAAGCTGTCTTCCTGAACCATAATCCTGGACTCTTCTAACCTCTCTACTCATCGCAAATAGAGTTCATTTTAGTGATTTGAAGGAAGATGGGACAAGTATTTTCAAACACCTGTAGGACAACATGGAAGTGGGAGGAGACTTCTACTGTAGCTCCCCAGAGAAGAGAGCTAGGGCTACAGAGTTGCAGTTACAAGGTTGCCCTCTCTGGCTTGATCCCCAAAGGAATTTTCTACTCCAAAATAGAATTTTTCTAGGATGCTATTTCTCAGTCCCTGGAGATACTCAAACAAAGGGCTTGTCACAAGGGTTTTTGTAGAAGCTATTCTTCACAGAGGTTGGGGGAGAGATTAAGCCAAAGGATCTCTGAGGTCTTTTTCAAATCTATAATTATGTGGCCTTTTGTTCATTGACTTCCATGTGTTCTAGTTGATCATTACAAACCTGGCAGGCCTTCTCAAGGGTTCAGTAATTAGCTGTCATTTCCCATTTGTCCAGAGAGTGTCCAACACAAAATACCCCTAAGATCTTGGCCAATAGAGAAATGTCATGGAATTTTAGAAATGACAGTATCTGCGGAGTTTATTCCAAGTTATATCATTTCAAAGATGAAGAAACCCAGGCTCAGAGGGAGCCATCACATCCACACCCTGTCACCCTTCGTGGCCAGTGCCAGACAGTAGCTAGTTGGATGCTAAAAGTAGAATTTAGATATCTTAACAATAAGCCCAGCAGTCTTTCAACTTCATTCGTAAATCATTTTTGTTTTGAGCATCTGTCACGTGGCAGCACTTGCCTGGATACTGGAGAGCTGAGAAGGAATGCGACAGGCAAGTCCTACTCTCACAGTGTATACATTCAGGAGGAACAAGACACACAGTGCCAAGTAAATAAAGTAGCTGAACTTCATCAAATGATTTTATTCTTAAAGTCATTAAAGCATGTAATGTTCCCCTTTTTTTGTTTCAGGGGTGTACAGATTGAAGAAGTGTAGGTGTTTATGTGGTTTTAGTGACAAACCCCATGTGCTTTCATTGATTTTATGTTTTATGTTAAAACATCAACCGCAAGGTAAAATGCATATTGTATGTTGTTGGATACGTACTTAACTGGTATGCATCCCATGTCTTTGGGTACTAGTGTATGAATTCTAATCTCTGTAAATGAAATGTTGTATGTGTTAATATATTTAATAGATGTAACTTAATAAACTGGCATTGAAGACTGAA (SEQ ID NO: 133) >NP_005109.2 tumor necrosis factor ligand superfamilymember 15 isoform VEGI-251 precursor [Homo sapiens]MAEDLGLSFGETASVEMLPEHGSCRPKARSSSARWALTCCLVLLPFLAGLTTYLLVSQLRAQGEACVQFQALKGQEFAPSHQQVYAPLRADGDKPRAHLTVVRQTPTQHFKNQFPALHWEHELGLAFTKNRMNYTNKFLLIPESGDYFIYSQVTFRGMTSECSEIRQAGRPNKPDSITVVITKVTDSYPEPTQLLMGTKSVCEVGSNWFQPIYLGAMFSLQEGDKLMVNVSDISLVDYTKEDKTFFGAFLL (SEQ ID NO: 134) Mouse TL1>NM_177371.4 Mus musculus tumor necrosis factor(ligand) superfamily, member 15 (Tnfsf15), mRNAATCAGAAGTCTCTCCAAGACAGCAGAAGGATGGCAGAGGAGCTGGGGTTGGGCTTCGGAGAAGGAGTCCCAGTGGAAGTGCTGCCGGAAGGCTGTAGACACAGGCCAGAGGCCAGGGCCGGGCTAGCTGCCAGGAGCAAAGCCTGCCTGGCTCTCACCTGCTGCCTGTTGTCATTTCCCATCCTCGCAGGACTTAGCACCCTCCTAATGGCTGGCCAGCTCCGGGTCCCCGGAAAAGACTGTATGCTTCGGGCCATAACAGAAGAGAGATCTGAGCCTTCACCACAGCAAGTTTACTCACCTCCCAGAGGCAAGCCGAGAGCACACCTGACAATTAAGAAACAAACCCCAGCACCACATCTGAAAAATCAGCTCTCTGCTCTACACTGGGAACATGACCTAGGGATGGCCTTCACCAAGAACGGGATGAAGTACATCAACAAATCCCTGGTGATCCCAGAGTCAGGAGACTATTTCATCTACTCCCAGATCACATTCCGAGGGACCACATCTGTGTGTGGTGACATCAGTCGGGGGAGACGACCAAACAAGCCAGACTCCATCACCATGGTTATCACCAAGGTAGCAGACAGCTACCCTGAGCCTGCCCGCCTACTAACAGGGTCCAAGTCTGTGTGTGAAATAAGCAACAACTGGTTCCAGTCCCTCTACCTTGGGGCCACGTTCTCCTTGGAAGAAGGAGACAGACTAATGGTAAACGTCAGTGACATCTCCTTGGTGGATTACACAAAAGAAGATAAAACTTTCTTTGGAGCTTTCTTGCTATAAGGAGGAGAAAACCATCATTCCAAGGGGCTCCCCTGCCTCCTACTTTCCAATTTCCTTTTCTCATATGGATCTATAAACAGGGGCTTTAGAGGGATCAGGGAAGGGGACAGTGGTTTAGCTATATAATTTAGGAACCCAATATTGATCCGTATATGCCTTATGGACTAAAATAGTAAATGGAAAACCCAGTACAGCTCATGTTTGATAGAGACCTGCTGGGTTTTAAAAATTGAAACACGCCTCATCCAATGGCACAATCTACTGATTTCAGGACAGAACCTTTCCACAGTGCCCTCTGTCCAAGTCCTTTCTGAATTCAGCAGTTCAGTTAGAGCTGAATTCGACAATGAACTTACTCCAGATCAAGAGCTAAAGACAGAATCCAAAGAAAGACTGAGAAAATGATGTTATTTCTCCAAGAGGCAATGCATTTCCACATTCTTTTGTGCCTAACCTAAAAAATAAGAAAGAAGAAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGGACAAGAAAAGACAAGACAAGACAAGAAAAAAGAAAAAATGGTATTTCTCGTGAATATTCCCTAAAAGGAATTGGTTTTCTGCTGTGAAGGAGAAACCTCACCTTTCTTCTGATTGCATCCTTTAGTATCCAAACATACAAGTGGGAATTCCAAATGCACATGGAACATAGAACACTTTTATTATTGTGAGAACATGTTTATTGAGTACCTACTATGCTCTGGGCACTCAGCCCACAGGACCATGAAGAGAAAGTCAAATTTTCTTAAAAACTAAATGAATCCTCAATACATACTTCCTGATCAACTACCACTCAAAATGTATAACTTCCAAAGTATAACTTCAAGTCAGCCATCTAGGTGGTTTCTTGGGTAAAGGTGCTTGTCATTAAGCCTGACACCTGGGTTTGACCTCCCAGAACCCAAAAGCTGGAAGGAGAGAATTGGTTCCCACAAATTATCCTCAAACCCCCATACAAATGATGTGGCATGCACACATGTAACTAAATAAATAAGTGTAAAACAAAAACAAAAACAAAATTTTAAAGAAAAATTTCAAGTCCTGAAAGACAGCATTCCTGAGAATGTTGTCTCCATCGTTGTCCAGTATAGGCTAACCAGCTGATAGAGACACTGAAGGAATTTAAAGACAGACATCAAGTGAAATGGAGCACTGTAGAAACACTTGATTCATGCCAGGAGTCAATGTACTATGAAGACCAACAACAAAGTGTCAGTCATCAAATCCAGAGGTGTTTATCTAGATCTGCTTTCAAGTTTGGTTTGCAGCCTTTATATAGTCTCTATTACAAATGCTCGTGTCATGGTAGATGCCACAAGGAGTCAGAGGGTAAACTTAGCCCCAAACCACTGCTGAGCCATCTTCTAGGAAACCTTCGAAGCAGAGCTGGGCAGCGTGACTCCCACACAATGACTGGGAAAGTAGTAGCTGATCAAAATTTGTTGAGTAATAATTTGTTAGAAAATTCATCTCCACTGCCTACTAAACCTAAGTTGTATACTATCTAGCTTCTGCTAAGCCAACTTACATTGGCCACTTTTTCTGTCTTCAACTTCTTGAAGTATCACAGGTCTCAGTGAGAACACAGGGAAAGGTGAGGTCGCCTTCCCCTGGTTCTTCATAGGGGAAACCACACCTGAAAGAAGATGAGCAGCCTGAGGTGACCTGGAGGAAGGGCTGTCTCAGAAGAAGGACTTATTTTTTGGCTTAGGTCTAAAACCTTGAGAGTAATGCTCACTGGTCAATTGAGGATGCTTTATCAATGACTCCAGTCTGACTCCAAGGTCAGAAAGGAGAGTGAGATGCTCTCTCTGCCTGCATATATCTTCATGGAACATGAGAATATTGAGCAACATAGACTTATAGGAAAACACTTGCCCAAAAGTAGCCAGAGTGACCTGGTCATCCCCTCTACTAAACCCAAGCTTTGTGTCAAGGGCCTTCAAAGCTGCCCAGAAGTGATCTGGATGGCTTGGGAATTTATCCAAGACAGGAATTTCCTGACAGCCAAAGATGCTTGAGTCCTTGTGCCTGACATGCATTTATTTTGCCCCTGTTTATTGAAGACTGTAACTGTTGATTTGTGGGTATACATACATACATACATACATACATACATACATACATACATATGCTGTCATGAAGGCAGCATCAAACATTACTAATTGGACTCAAACCAGCATTTCTGTTTCCAAGATACTAAGTATTCCCATGCAAACAGGAGCATGCTATTTTTCTAAAGCAAAATGAAAAAAATAGTTTTGAAAGTATATATATGATGGAGTCAAGTGTAATGGCATACATCTGTAAACCCAGCACATGGGATGCTGAGCCAGGAGGATTGCCGTGAGTTTGAGGAGAACAGGGGCTAAATAGTAATTTTCAGGAAAGCCTTGCCTATATAACAAGACCTTGTCTCAAATGAAAAAAAAAAAAAAAATAGACCCCAGGCTGGTCCTTGGAGATAAGGTAATATATTCATTGGGTGAGGGGGTGTGTGTTTTGGAAAATAGTTAATTTAGTGAGAAATGCTTTTCGGTCAAATGCATCTCAAAGGCTGCTGAATTCAAATCGGGTCTGTAAATGCTTACCTAGTGCTTGCTTGCCCTGGGGACAGAGACATAAATTACTTTAGTCTCAGATCCACTCGTTCTAACAGATTGGCATCTCCATCGTCTGTGGAGCTTTTAATCACTCTGTTTGTATTAGCTAATTAATTAGCTAACTTGAGACACACTGATATTTTCTTATTATAAACATGGGTGCCATTTGATAAAAGACAATCATTAACAAAATGGTTCGAATTTCCGCTTAAGTGATCTTCTTTTTTCCTTTTCATTTTTTTTAACTAGCTAATCAAAGGTAGTTTCCCAAAAATAAATGCAAAGGGAGTATAAAGAAAAAATTCCCTGTGGTGGGAGCTAGTATTGAAACAACAGTATCAAAGAGGCTGTTACCTACTGGCCTCAAATTTTGGCAGGAACGCCTTTGAAAATGTTAGAACTTTACGGACAGCCTAGAGGTGCTTTGAAAAGTCTCTGTTGCCAACAAAAGCCATTAATCAGCATGCGGCACAGGTTACTCAAATTTTGACCTTGACTGTTTTTTAGATCTGTTACACAGAACACAACTTCTGGGCTGTAATCTCTGATGTGGATTTGGTGATTTACTAAGGTACCGTGGGAAACAAGGAAAGTGTACTTGTACCACATCGTTTCTCAGTGCATGTCAGAGTCTACTCAACAGCAGGGCATGCCAGAGCCTTGGATACATTCCGGGACAAACTATGTCACTCCTAAGGAAATTCCAAGTGTGTGCCTGTCAAGCACTCTGGATCATAGAAGCCCACGAGTTCACTGTGCACAAGGCACAGCCATGGCCAGCACTCTCTTGCATGGTATTTCTCTTAAGCTCTTACTCAATCACGGTCCCATGATTGTGACATTGGGGATTAATTGCTTGAGCAGGTTTATTTACAGTCTGTTCCTTGCAAAATACATGCAGATATGTCTGGCCTCAAAATCCCCTGATTGTTTTAGGGCTTAGAGAATACTGGGGATGTTTTTGCTGTTTTCAGATGTACTTTATTTAAGCTTGCAGAATTACCCTGAATATTAACAGTGTTCTAAGATATTGCCTGCTAGCTTCTGGCTAATTTACTAGTGGTGACAGTATCAGATCAGAGTATCTATATTTATGTCTTGCTATTATAGTTAAAACTTCCTGATCTCTGTAACACACTCACCCCTACCTCATCTATCTACCCATCTTGTGGATGTAGCTGTGAGAAGACTCACAAGCCCGAGTTGCAGTTACTTTTCTGAAGCAACATAGTATGTTAATGGAATGGCCAGAACTCTACTCTTGGCACATGGCACTGAATTTGATGCCACTAAAAGAAAAATTGAAGGCAGAAATATTTTTTACTATGCATGGGACAACGTAGAAGAGCAAGGAGACTGCTTACACATGGTGGTCACATCTCTGGCTTCATCCCTAAACCAATTTTCTGACCCCAAGTCGATTTTTTTTCATGTAGTTATTGTTCATTTTCTGGAAAGAGTCAAGCAAAAAGAGAGTTTTATAGAAACCATTGCATCATGGAGGTCAGGGGAGGGATTAAGCCAAAGAATTCCTTCTCCAAATCTATAGCCATATGGCCACCCTTTGGTGTACTTCTATTTGATCATGACAAACCTGAGAGCCCTGCCCAGAGTTCAGTGGATCCTAATGAACTCCAAGAGTAATTCATTCCCTCACCAACTCTAGGGGCTTGGCCAGTGCAGAAAATGTCATGGGATTTTAAAGTTAACATGAGCTGCTATCCAAACTTATGTCTCTTTAAGAATGGAGAGACACAGGCCAGGAGAGGTAACATATGAAGCCTGGTATTGGGCAGTAGCTTGATGGAGTATTGAGGCTAAAAGTAGACTTCCTGCCCCTGACCATACACAACACCCTTTCAGTTTGATCCATGGTGGTCTTATTCTACTTTATTTTGAGCACCTGTCACACCTAGTTACTGTCATGCCAAGAAGGTCCATAACAGGCAAATCCTACTCTGCTGTGTGCACACAAGAGGAAGGAGGCTCACAGTAGCAAGTAAACAGATAAGCAAACGTACACGATTTTCGTCTTAAAGTCATTAAGACACACGCGTACCCCTCTTTTGTTTCAGAGGGTATACAGGCTGAACAGATGTCAGTGTTCACCTATTCTTATTGATAAGCCCCATGTGCTTTCATTGGTTGAATGTTTTATGTTAAAACGTCATATTGCCATCGTAAAATGCATATTGTATGTTGTTGGGTATATAATTAACTAATATGCATCGCATGTATGAATTCTAATCTCTGTAAATGAAAACTTATATATGTTAACATATGTAATAGTTATAATTTAATAAACTGACACTGGAGACTAC(SEQ ID NO: 135) >NP_796345.4 tumor necrosis factor ligand superfamilymember 15 [Mus musculus]MAEELGLGFGEGVPVEVLPEGCRHRPEARAGLAARSKACLALTCCLLSFPILAGLSTLLMAGQLRVPGKDCMLRAITEERSEPSPQQVYSPPRGKPRAHLTIKKQTPAPHLKNQLSALHWEHDLGMAFTKNGMKYINKSLVIPESGDYFIYSQITFRGTTSVCGDISRGRRPNKPDSITMVITKVADSYPEPARLLTGSKSVCEISNNWFQSLYLGATFSLEEGDRLMVNVSDISLVDYTKEDKTFFGAFLL (SEQ ID NO: 136) Human CD80>NM_005191.4 Homo sapiens CD80 molecule (CD80), mRNAAAACCCTCTGTAAAGTAACAGAAGTTAGAAGGGGAAATGTCGCCTCTCTGAAGATTACCCAAAGAAAAAGTGATTTGTCATTGCTTTATAGACTGTAAGAAGAGAACATCTCAGAAGTGGAGTCTTACCCTGAAATCAAAGGATTTAAAGAAAAAGTGGAATTTTTCTTCAGCAAGCTGTGAAACTAAATCCACAACCTTTGGAGACCCAGGAACACCCTCCAATCTCTGTGTGTTTTGTAAACATCACTGGAGGGTCTTCTACGTGAGCAATTGGATTGTCATCAGCCCTGCCTGTTTTGCACCTGGGAAGTGCCCTGGTCTTACTTGGGTCCAAATTGTTGGCTTTCACTTTTGACCCTAAGCATCTGAAGCCATGGGCCACACACGGAGGCAGGGAACATCACCATCCAAGTGTCCATACCTCAATTTCTTTCAGCTCTTGGTGCTGGCTGGTCTTTCTCACTTCTGTTCAGGTGTTATCCACGTGACCAAGGAAGTGAAAGAAGTGGCAACGCTGTCCTGTGGTCACAATGTTTCTGTTGAAGAGCTGGCACAAACTCGCATCTACTGGCAAAAGGAGAAGAAAATGGTGCTGACTATGATGTCTGGGGACATGAATATATGGCCCGAGTACAAGAACCGGACCATCTTTGATATCACTAATAACCTCTCCATTGTGATCCTGGCTCTGCGCCCATCTGACGAGGGCACATACGAGTGTGTTGTTCTGAAGTATGAAAAAGACGCTTTCAAGCGGGAACACCTGGCTGAAGTGACGTTATCAGTCAAAGCTGACTTCCCTACACCTAGTATATCTGACTTTGAAATTCCAACTTCTAATATTAGAAGGATAATTTGCTCAACCTCTGGAGGTTTTCCAGAGCCTCACCTCTCCTGGTTGGAAAATGGAGAAGAATTAAATGCCATCAACACAACAGTTTCCCAAGATCCTGAAACTGAGCTCTATGCTGTTAGCAGCAAACTGGATTTCAATATGACAACCAACCACAGCTTCATGTGTCTCATCAAGTATGGACATTTAAGAGTGAATCAGACCTTCAACTGGAATACAACCAAGCAAGAGCATTTTCCTGATAACCTGCTCCCATCCTGGGCCATTACCTTAATCTCAGTAAATGGAATTTTTGTGATATGCTGCCTGACCTACTGCTTTGCCCCAAGATGCAGAGAGAGAAGGAGGAATGAGAGATTGAGAAGGGAAAGTGTACGCCCTGTATAACAGTGTCCGCAGAAGCAAGGGGCTGAAAAGATCTGAAGGTCCCACCTCCATTTGCAATTGACCTCTTCTGGGAACTTCCTCAGATGGACAAGATTACCCCACCTTGCCCTTTACGTATCTGCTCTTAGGTGCTTCTTCACTTCAGTTGCTTTGCAGGAAGTGTCTAGAGGAATATGGTGGGCACAGAAGTAGCTCTGGTGACCTTGATCAAGGTGTTTTGAAATGCAGAATTCTTGAGTTCTGGAAGGGACTTTAGAGAATACCAGTGTTATTAATGACAAAGGCACTGAGGCCCAGGGAGGTGACCCGAATTATAAAGGCCAGCGCCAGAACCCAGATTTCCTAACTCTGGTGCTCTTTCCCTTTATCAGTTTGACTGTGGCCTGTTAACTGGTATATACATATATATGTCAGGCAAAGTGCTGCTGGAAGTAGAATTTGTCCAATAACAGGTCAACTTCAGAGACTATCTGATTTCCTAATGTCAGAGTAGAAGATTTTATGCTGCTGTTTACAAAAGCCCAATGTAATGCATAGGAAGTATGGCATGAACATCTTTAGGAGACTAATGGAAATATTATTGGTGTTTACCCAGTATTCCATTTTTTTCATTGTGTTCTCTATTGCTGCTCTCTCACTCCCCCATGAGGTACAGCAGAAAGGAGAACTATCCAAAACTAATTTCCTCTGACATGTAAGACGAATGATTTAGGTACGTCAAAGCAGTAGTCAAGGAGGAAAGGGATAGTCCAAAGACTTAACTGGTTCATATTGGACTGATAATCTCTTTAAATGGCTTTATGCTAGTTTGACCTCATTTGTAAAATATTTATGAGAAAGTTCTCATTTAAAATGAGATCGTTGTTTACAGTGTATGTACTAAGCAGTAAGCTATCTTCAAATGTCTAAGGTAGTAACTTTCCATAGGGCCTCCTTAGATCCCTAAGATGGCTTTTTCTCCTTGGTATTTCTGGGTCTTTCTGACATCAGCAGAGAACTGGAAAGACATAGCCAACTGCTGTTCATGTTACTCATGACTCCTTTCTCTAAAACTGCCTTCCACAATTCACTAGACCAGAAGTGGACGCAACTTAAGCTGGGATAATCACATTATCATCTGAAAATCTGGAGTTGAACAGCAAAAGAAGACAACATTTCTCAAATGCACATCTCATGGCAGCTAAGCCACATGGCTGGGATTTAAAGCCTTTAGAGCCAGCCCATGGCTTTAGCTACCTCACTATGCTGCTTCACAAACCTTGCTCCTGTGTAAAACTATATTCTCAGTGTAGGGCAGAGAGGTCTAACACCAACATAAGGTACTAGCAGTGTTTCCCGTATTGACAGGAATACTTAACTCAATAATTCTTTTCTTTTCCATTTAGTAACAGTTGTGATGACTATGTTTCTATTCTAAGTAATTCCTGTATTCTACAGCAGATACTTTGTCAGCAATACTAAGGGAAGAAACAAAGTTGAACCGTTTCTTTAATAA (SEQ ID NO: 137) >NP__005182.1 T-lymphocyte activation antigen CD80precursor [Homo sapiens]MGHTRRQGTSPSKCPYLNFFQLLVLAGLSHFCSGVIHVTKEVKEVATLSCGHNVSVEELAQTRIYWQKEKKMVLTMMSGDMNIWPEYKNRTIFDITNNLSIVILALRPSDEGTYECVVLKYEKDAFKREHLAEVTLSVKADFPTPSISDFEIPTSNIRRIICSTSGGFPEPHLSWLENGEELNAINTTVSQDPETELYAVSSKLDFNMTTNHSFMCLIKYGHLRVNQTFNWNTTKQEHFPDNLLPSWAITLISVNGIFVICCLTYCFAPRCRERRRNERLRRESVRPV (SEQ ID NO: 138) Mouse CD80>NM_009855.2 Mus musculus CD80 antigen (Cd80),transcript variant 2, mRNAGAGTTTTATACCTCAATAGACTCTTACTAGTTTCTCTTTTTCAGGTTGTGAAACTCAACCTTCAAAGACACTCTGTTCCATTTCTGTGGACTAATAGGATCATCTTTAGCATCTGCCGGGTGGATGCCATCCAGGCTTCTTTTTCTACATCTCTGTTTCTCGATTTTTGTGAGCCTAGGAGGTGCCTAAGCTCCATTGGCTCTAGATTCCTGGCTTTCCCCATCATGTTCTCCAAAGCATCTGAAGCTATGGCTTGCAATTGTCAGTTGATGCAGGATACACCACTCCTCAAGTTTCCATGTCCAAGGCTCATTCTTCTCTTTGTGCTGCTGATTCGTCTTTCACAAGTGTCTTCAGATGTTGATGAACAACTGTCCAAGTCAGTGAAAGATAAGGTATTGCTGCCTTGCCGTTACAACTCTCCTCATGAAGATGAGTCTGAAGACCGAATCTACTGGCAAAAACATGACAAAGTGGTGCTGTCTGTCATTGCTGGGAAACTAAAAGTGTGGCCCGAGTATAAGAACCGGACTTTATATGACAACACTACCTACTCTCTTATCATCCTGGGCCTGGTCCTTTCAGACCGGGGCACATACAGCTGTGTCGTTCAAAAGAAGGAAAGAGGAACGTATGAAGTTAAACACTTGGCTTTAGTAAAGTTGTCCATCAAAGCTGACTTCTCTACCCCCAACATAACTGAGTCTGGAAACCCATCTGCAGACACTAAAAGGATTACCTGCTTTGCTTCCGGGGGTTTCCCAAAGCCTCGCTTCTCTTGGTTGGAAAATGGAAGAGAATTACCTGGCATCAATACGACAATTTCCCAGGATCCTGAATCTGAATTGTACACCATTAGTAGCCAACTAGATTTCAATACGACTCGCAACCACACCATTAAGTGTCTCATTAAATATGGAGATGCTCACGTGTCAGAGGACTTCACCTGGGAAAAACCCCCAGAAGACCCTCCTGATAGCAAGAACACACTTGTGCTCTTTGGGGCAGGATTCGGCGCAGTAATAACAGTCGTCGTCATCGTTGTCATCATCAAATGCTTCTGTAAGCACAGAAGCTGTTTCAGAAGAAATGAGGCAAGCAGAGAAACAAACAACAGCCTTACCTTCGGGCCTGAAGAAGCATTAGCTGAACAGACCGTCTTCCTTTAGTTCTTCTCTGTCCATGTGGGATACATGGTATTATGTGGCTCATGAGGTACAATCTTTCTTTCAGCACCGTGCTAGCTGATCTTTCGGACAACTTGACACAAGATAGAGTTAACTGGGAAGAGAAAGCCTTGAATGAGGATTTCTTTCCATCAGGAAGCCTACGGGCAAGTTTGCTGGGCCTTTGATTGCTTGATGACTGAAGTGGAAAGGCTGAGCCCACTGTGGGTGGTGCTAGCCCTGGGCAGGGGCAGGTGACCCTGGGTGGTATAAGAAAAAGAGCTGTCACTAAAAGGAGAGGTGCCTAGTCTTACTGCAACTTGATATGTCATGTTTGGTTGGTGTCTGTGGGAGGCCTGCCCTTTTCTGAAGAGAAGTGGTGGGAGAGTGGATGGGGTGGGGGCAGAGGAAAAGTGGGGGAGAGGGCCTGGGAGGAGAGGAGGGAGGGGGACGGGGTGGGGGTGGGGAAAACTATGGTTGGGATGTAAAAACGATAATAATATAAATATTAAATAAAAAGAGAGTATTGAGCAAA (SEQ ID NO: 139) >NP_033985.3 T-lymphocyte activation antigen CD80precursor [Mus musculus]MACNCQLMQDTPLLKFPCPRLILLFVLLIRLSQVSSDVDEQLSKSVKDKVLLPCRYNSPHEDESEDRIYWQKHDKVVLSVIAGKLKVWPEYKNRTLYDNTTYSLIILGLVLSDRGTYSCVVQKKERGTYEVKHLALVKLSIKADFSTPNITESGNPSADTKRITCFASGGFPKPRFSWLENGRELPGINTTISQDPESELYTISSQLDFNTTRNHTIKCLIKYGDAHVSEDFTWEKPPEDPPDSKNTLVLFGAGFGAVITVVVIVVIIKCFCKHRSCFRRNEASRETNNSLTFGPEEALAEQTVFL (SEQ ID NO: 140) Human CD86>NM_175862.5 Homo sapiens CD86 molecule (CD86),transcript variant 1, mRNAAGTCATTGCCGAGGAAGGCTTGCACAGGGTGAAAGCTTTGCTTCTCTGCTGCTGTAACAGGGACTAGCACAGACACACGGATGAGTGGGGTCATTTCCAGATATTAGGTCACAGCAGAAGCAGCCAAAATGGATCCCCAGTGCACTATGGGACTGAGTAACATTCTCTTTGTGATGGCCTTOCTGOTCTCTGGTGCTGCTCCTCTGAAGATTCAAGCTTATTTCAATGAGACTGCAGACCTGCCATGCCAATTTGCAAACTCTCAAAACCAAAGCCTGAGTGAGCTAGTAGTATTTTGGCAGGACCAGGAAAACTTGGTTCTGAATGAGGTATACTTAGGCAAAGAGAAATTTGACAGTGTTCATTCCAAGTATATGGGCCGCACAAGTTTTGATTCGGACAGTTGGACCCTGAGACTTCACAATCTTCAGATCAAGGACAAGGGCTTGTATCAATGTATCATCCATCACAAAAAGCCCACAGGAATGATTCGCATCCACCAGATGAATTCTGAACTGTCAGTGCTTGCTAACTTCAGTCAACCTGAAATAGTACCAATTTCTAATATAACAGAAAATGTGTACATAAATTTGACCTGCTCATCTATACACGGTTACCCAGAACCTAAGAAGATGAGTGTTTTGCTAAGAACCAAGAATTCAACTATCGAGTATGATGGTGTTATGCAGAAATCTCAAGATAATGTCACAGAACTGTACGACGTTTCCATCAGCTTGTCTGTTTCATTCCCTGATGTTACGAGCAATATGACCATCTTCTGTATTCTGGAAACTGACAAGACGCGGCTTTTATCTTCACCTTTCTCTATAGAGCTTGAGGACCCTCAGCCTCCCCCAGACCACATTCCTTGGATTACAGCTGTACTTCCAACAGTTATTATATGTGTGATGGTTTTCTGTCTAATTCTATGGAAATGGAAGAAGAAGAAGCGGCCTCGCAACTCTTATAAATGTGGAACCAACACAATGGAGAGGGAAGAGAGTGAACAGACCAAGAAAAGAGAAAAAATCCATATACCTGAAAGATCTGATGAAGCCCAGCGTGTTTTTAAAAGTTCGAAGACATCTTCATGCGACAAAAGTGATACATGTTTTTAATTAAAGAGTAAAGCCCATACAAGTATTCATTTTTTCTACCCTTTCCTTTGTAAGTTCCTGGGCAACCTTTTTGATTTCTTCCAGAAGGCAAAAAGACATTACCATGAGTAATAAGGGGGCTCCAGGACTCCCTCTAAGTGGAATAGCCTCCCTGTAACTCCAGCTCTGCTCCGTATGCCAAGAGGAGACTTTAATTCTCTTACTGCTTCTTTTCACTTCAGAGCACACTTATGGGCCAAGCCCAGCTTAATGGCTCATGACCTGGAAATAAAATTTAGGACCAATACCTCCTCCAGATCAGATTCTTCTCTTAATTTCATAGATTGTGTTTTTTTTTTAAATAGACCTCTCAATTTCTGGAAAACTGCCTTTTATCTGCCCAGAATTCTAAGCTGGTGCCCCACTGAATTTTGTGTGTACCTGTGACTAAACAACTACCTCCTCAGTCTGGGTGGGACTTATGTATTTATGACCTTATAGTGTTAATATCTTGAAACATAGAGATCTATGTACTGTAATAGTGTGATTACTATGCTCTAGAGAAAAGTCTACCCCTGCTAAGGAGTTCTCATCCCTCTGTCAGGGTCAGTAAGGAAAACGGTGGCCTAGGGTACAGGCAACAATGAGCAGACCAACCTAAATTTGGGGAAATTAGGAGAGGCAGAGATAGAACCTGGAGCCACTTCTATCTGGGCTGTTGCTAATATTGAGGAGGCTTGCCCCACCCAACAAGCCATAGTGGAGAGAACTGAATAAACAGGAAAATGCCAGAGCTTGTGAACCCTGTTTCTCTTGAAGAACTGACTAGTGAGATGGCCTGGGGAAGCTGTGAAAGAACCAAAAGAGATCACAATACTCAAAAGAGAGAGAGAGAGAAAAAAGAGAGATCTTGATCCACAGAAATACATGAAATGTCTGGTCTGTCCACCCCATCAACAAGTCTTGAAACAAGCAACAGATGGATAGTCTGTCCAAATGGACATAAGACAGACAGCAGTTTCCCTGGTGGTCAGGGAGGGGTTTTGGTGATACCCAAGTTATTGGGATGTCATCTTCCTGGAAGCAGAGCTGGGGAGGGAGAGCCATCACCTTGATAATGGGATGAATGGAAGGAGGCTTAGGACTTTCCACTCCTGGCTGAGAGAGGAAGAGCTGCAACGGAATTAGGAAGACCAAGACACAGATCACCCGGGGCTTACTTAGCCTACAGATGTCCTACGGGAACGTGGGCTGGCCCAGCATAGGGCTAGCAAATTTGAGTTGGATGATTGTTTTTGCTCAAGGCAACCAGAGGAAACTTGCATACAGAGACAGATATACTGGGAGAAATGACTTTGAAAACCTGGCTCTAAGGTGGGATCACTAAGGGATGGGGCAGTCTCTGCCCAAACATAAAGAGAACTCTGGGGAGCCTGAGCCACAAAAATGTTCCTTTATTTTATGTAAACCCTCAAGGGTTATAGACTGCCATGCTAGACAAGCTTGTCCATGTAATATTCCCATGTTTTTACCCTGCCCCTGCCTTGATTAGACTCCTAGCACCTGGCTAGTTTCTAACATGTTTTGTGCAGCACAGTTTTTAATAAATGCTTGTTACATTCA (SEQ ID NO: 141) >NP_787058.5 T-lymphocyte activation antigen CD86isoform 1 precursor [Homo sapiens]MDPQCTMGLSNILFVMAFLLSGAAPLKIQAYFNETADLPCQFANSQNQSLSELVVFWQDQENLVLNEVYLGKEKFDSVHSKYMGRTSFDSDSWTLRLHNLQIKDKGLYQCIIHHKKPTGMIRIHQMNSELSVLANFSQPEIVPISNITENVYINLTCSSIHGYPEPKKMSVLLRTKNSTIEYDGVMQKSQDNVTELYDVSISLSVSFPDVTSNMTIFCILETDKTRLLSSPFSIELEDPQPPPDHIPWITAVLPTVIICVMVFCLILWKWKKKKRPRNSYKCGTNTMEREESEQTKKREKIHIPERSDEAQRVFKSSKTSSCDKSDTCF (SEQ ID NO: 142) Mouse CD86>NM_019388.3 Mus musculus CD86 antigen (Cd86), mRNAATTGCTGAGGAAGAAAGAGGAGCAAGCAGACGCGTAAGAGTGGCTCCTGTAGGCAGCACGGACTTGAACAACCAGACTCCTGTAGACGTGTTCCAGAACTTACGGAAGCACCCACGATGGACCCCAGATGCACCATGGGCTTGGCAATCCTTATCTTTGTGACAGTCTTGCTGATCTCAGATGCTGTTTCCGTGGAGACGCAAGCTTATTTCAATGGGACTGCATATCTGCCGTGCCCATTTACAAAGGCTCAAAACATAAGCCTGAGTGAGCTGGTAGTATTTTGGCAGGACCAGCAAAAGTTGGTTCTGTACGAGCACTATTTGGGCACAGAGAAACTTGATAGTGTGAATGCCAAGTACCTGGGCCGCACGAGCTTTGACAGGAACAACTGGACTCTACGACTTCACAATGTTCAGATCAAGGACATGGGCTCGTATGATTGTTTTATACAAAAAAAGCCACCCACAGGATCAATTATCCTCCAACAGACATTAACAGAACTGTCAGTGATCGCCAACTTCAGTGAACCTGAAATAAAACTGGCTCAGAATGTAACAGGAAATTCTGGCATAAATTTGACCTGCACGTCTAAGCAAGGTCACCCGAAACCTAAGAAGATGTATTTTCTGATAACTAATTCAACTAATGAGTATGGTGATAACATGCAGATATCACAAGATAATGTCACAGAACTGTTCAGTATCTCCAACAGCCTCTCTCTTTCATTCCCGGATGGTGTGTGGCATATGACCGTTGTGTGTGTTCTGGAAACGGAGTCAATGAAGATTTCCTCCAAACCTCTCAATTTCACTCAAGAGTTTCCATCTCCTCAAACGTATTGGAAGGAGATTACAGCTTCAGTTACTGTGGCCCTCCTCCTTGTGATGCTGCTCATCATTGTATGTCACAAGAAGCCGAATCAGCCTAGCAGGCCCAGCAACACAGCCTCTAAGTTAGAGCGGGATAGTAACGCTGACAGAGAGACTATCAACCTGAAGGAACTTGAACCCCAAATTGCTTCAGCAAAACCAAATGCAGAGTGAAGGCAGTGAGAGCCTGAGGAAAGAGTTAAAAATTGCTTTGCCTGAAATAAGAAGTGCAGAGTTTCTCAGAATTCAAAAATGTTCTCAGCTGATTGGAATTCTACAGTTGAATAATTAAAGAACAAAATACACAACAGTGTCCATATTTTATCCTGTTTCCTTTCCAAGTTTTTGGGCAATGTCAATTGTGTCCCCTATGCCAGGAGCAGACATCTATTTTGTCTTGCTTTGTTTAACTCAGTGCACACTCATAGGCCAAGAGCACTGAAATGGCTTCTTTCCCAGGAATAACATTTTGGATCAATCTCTCCTACTTGAGATCAGATTCTTCTTCTAATTTTGCATAGTGTGTTTTTATATGGAACTCCTTGTTGTAGGAATACTGGCTTTTATCTGTCTTGCACACTTGCATACTTATATACTTATACCTGGACAGCTACCTCTTCAGTCAGGATGGGAGTGGTATATTTGGTGATGTTATTTGATGTGTTCGTGTTGCTATCTTAAAACAGCAAAGAGCATATACTATAGTAGCTCAACTACAATGATCTAGAGAAAGACCCAGCACTTATAAGAAACACTGTCCCTCCATCAGGGTCAATAATGAATACAATGACCTAAGTAATATACAGGTGACAGCAACAGCACAGAGTTCTCAGTGCTGGCAAATCAAGAAACACAAATATGGAACCATCTCTAGATCCAAGAGCCACTCCTACCTGGGCTGCCACAGATACTGGAAGAATCCACCTGCCTGGCCAGCAAGTCACAACTTAGCAGGCAGCACTGAAGAAAGCAAGATGTACTGTATGCCCTTTTAAGAAAATGCCTGGAAAGGTCTGGAGAATGCTGTGCAAGGATAAGACAGCCAAGCACTCAAAACCAGGAGACATCACTAGAATCCAACCAACAAATGTTTATGGAAGGACTGATCTGCCCAGTCCATTGAAAAGTCAAGAGGTCAGAGATAGACCAGTGTGTGTCTCAATGGATGTAGATATCAGCCACCTCGGTGCTCAACAGGTATTTTATGATCTCCTTGTTTCAAATTCATCTAGATGTAGAACTAGGGAGAGAGCAGTCACATTGATGAAAGGCTAGGACTCTTTCAGCTCATGGCTTGTGTGGAAGGAGGGAAAGCAGAAATCACAACACTCTGAGACTACTGTAGTCTGCAGATACCTGAGTGGGTGTGGCTTGGCCTTTCAAAGGACAAAGAGCAACTAATGCTGAAAGCACATAGTGTATCTATACGGCATGGAATAGTCATCACCCAGACTTAAAGAGAACTTTGGCAGGTCTGAGCAGCAAAATATTGTTGTTTCCATTTTACATAAAGGGCCCTGGAGGGCTATAGACTATTCCGCTGGCAGGGCTCATGCTTGTAATGTGTCCATCTTGATTCACCCTGTGCAGACTCTTAAGATCTGGCCAGTTACCAACATGTTCTGTACAGAGTGGATTTCAATAAAGTTTTCTTGAATTTTTTCAAG(SEQ ID NO: 143) >NP_062261.3 T-lymphocyte activation antigen 0D86precursor [Mus musculus]MDPRCTMGLAILIFVTVLLISDAVSVETQAYFNGTAYLPCPFTKAQNISLSELVVFWQDQQKLVLYEHYLGTEKLDSVNAKYLGRTSFDRNNWTLRLHNVQIKDMGSYDCFIQKKPPTGSIILQQTLTELSVIANFSEPEIKLAQNVTGNSGINLTCTSKQGHPKPKKMYFLITNSTNEYGDNMQISQDNVTELFSISNSLSLSFPDGVWHMTVVCVLETESMKISSKPLNFTQEFPSPQTYWKEITASVTVALLLVMLLIIVCHKKPNQPSRPSNTASKLERDSNADRETINLKELEPQIASAKPNAE (SEQ ID NO: 144)Human LFA-3 >NM_001779.3 Homo sapiens CD58 molecule (CD58), (CD58)transcript variant 1, mRNAGAACTTAGGGCTGCTTGTGGCTGGGCACTCGCGCAGAGGCCGGCCCGACGAGCCATGGTTGCTGGGAGCGACGCGGGGCGGGCCCTGGGGGTCCTCAGCGTGGTCTGCCTGCTGCACTGCTTTGGTTTCATCAGCTGTTTTTCCCAACAAATATATGGTGTTGTGTATGGGAATGTAACTTTCCATGTACCAAGCAATGTGCCTTTAAAAGAGGTCCTATGGAAAAAACAAAAGGATAAAGTTGCAGAACTGGAAAATTCTGAATTCAGAGCTTTCTCATCTTTTAAAAATAGGGTTTATTTAGACACTGTGTCAGGTAGCCTCACTATCTACAACTTAACATCATCAGATGAAGATGAGTATGAAATGGAATCGCCAAATATTACTGATACCATGAAGTTCTTTCTTTATGTGCTTGAGTCTCTTCCATCTCCCACACTAACTTGTGCATTGACTAATGGAAGCATTGAAGTCCAATGCATGATACCAGAGCATTACAACAGCCATCGAGGACTTATAATGTACTCATGGGATTGTCCTATGGAGCAATGTAAACGTAACTCAACCAGTATATATTTTAAGATGGAAAATGATCTTCCACAAAAAATACAGTGTACTCTTAGCAATCCATTATTTAATACAACATCATCAATCATTTTGACAACCTGTATCCCAAGCAGCGGTCATTCAAGACACAGATATGCACTTATACCCATACCATTAGCAGTAATTACAACATGTATTGTGCTGTATATGAATGGTATTCTGAAATGTGACAGAAAACCAGACAGAACCAACTCCAATTGATTGGTAACAGAAGATGAAGACAACAGCATAACTAAATTATTTTAAAAACTAAAAAGCCATCTGATTTCTCATTTGAGTATTACAATTTTTGAACAACTGTTGGAAATGTAACTTGAAGCAGCTGCTTTAAGAAGAAATACCCACTAACAAAGAACAAGCATTAGTTTTGGCTGTCATCAACTTATTATATGACTAGGTGCTTGCTTTTTTTGTCAGTAAATTGTTTTTACTGATGATGTAGATACTTTTGTAAATAAATGTAAATATGTACACAAGTGA (SEQ ID NO: 145) >NP_001770.1 lymphocyte function-associated antigen 3isoform 1 [Homo sapiens]MVAGSDAGRALGVLSVVCLLHCFGFISCFSQQIYGVVYGNVTFHVPSNVPLKEVLWKKQKDKVAELENSEFRAFSSFKNRVYLDTVSGSLTIYNLTSSDEDEYEMESPNITDTMKFFLYVLESLPSPTLTCALTNGSIEVQCMIPEHYNSHRGLIMYSWDCPMEQCKRNSTSIYFKMENDLPQKIQCTLSNPLFNTTSSIILTTCIPSSGHSRHRYALIPIPLAVITTCIVLYMNGILKCDRKPDRTNSN (SEQ ID NO: 146) Human SLAM>NM_003037.5 Homo sapiens signaling lymphocytic (CD150)activation molecule family member 1 (SLAMF1), transcript variant 1, mRNAAGACAGCCTCTGCTGCATGACACGAAGCTTGCTTCTGCCTGGCATCTGTGAGCAGCTGCCAGGCTCCGGCCAGGATCCCTTCCTTCTCCTCATTGGCTGATGGATCCCAAGGGGCTCCTCTCCTTGACCTTCGTGCTGTTTCTCTCCCTGGCTTTTGGGGCAAGCTACGGAACAGGTGGGCGCATGATGAACTGCCCAAAGATTCTCCGGCAGTTGGGAAGCAAAGTGCTGCTGCCCCTGACATATGAAAGGATAAATAAGAGCATGAACAAAAGCATCCACATTGTCGTCACAATGGCAAAATCACTGGAGAACAGTGTCGAGAACAAAATAGTGTCTCTTGATCCATCCGAAGCAGGCCCTCCACGTTATCTAGGAGATCGCTACAAGTTTTATCTGGAGAATCTCACCCTGGGGATACGGGAAAGCAGGAAGGAGGATGAGGGATGGTACCTTATGACCCTGGAGAAAAATGTTTCAGTTCAGCGCTTTTGCCTGCAGTTGAGGCTTTATGAGCAGGTCTCCACTCCAGAAATTAAAGTTTTAAACAAGACCCAGGAGAACGGGACCTGCACCTTGATACTGGGCTGCACAGTGGAGAAGGGGGACCATGTGGCTTACAGCTGGAGTGAAAAGGCGGGCACCCACCCACTGAACCCAGCCAACAGCTCCCACCTCCTGTCCCTCACCCTCGGCCCCCAGCATGCTGACAATATCTACATCTGCACCGTGAGCAACCCTATCAGCAACAATTCCCAGACCTTCAGCCCGTGGCCCGGATGCAGGACAGACCCCTCAGAAACAAAACCATGGGCAGTGTATGCTGGGCTGTTAGGGGGTGTCATCATGATTCTCATCATGGTGGTAATACTACAGTTGAGAAGAAGAGGTAAAACGAACCATTACCAGACAACAGTGGAAAAAAAAAGCCTTACGATCTATGCCCAAGTCCAGAAACCAGGTCCTCTTCAGAAGAAACTTGACTCCTTCCCAGCTCAGGACCCTTGCACCACCATATATGTTGCTGCCACAGAGCCTGTCCCAGAGTCTGTCCAGGAAACAAATTCCATCACAGTCTATGCTAGTGTGACACTTCCAGAGAGCTGACACCAGAGACCAACAAAGGGACTTTCTGAAGGAAAATGGAAAAACCAAAATGAACACTGAACTTGGCCACAGGCCCCAAGTTTCCTCTGGCAGACATGCTGCACGTCTGTACCCTTCTCAGATCAACTCCCTGGTGATGTTTCTTCCACATACATCTGTGAAATGAACAAGGAAGTGAGGCTTCCCAAGAATTTAGCTTGCTGTGCAGTGGCTGCAGGCGCAGAACAGAGCGTTACTTGATAACAGCGTTCCATCTTTGTGTTGTAGCAGATGAAATGGACAGTAATGTGAGTTCAGACTTTGGGCATCTTGCTCTTGGCTGGAACTGGATAATAAAAATCAGACTGAAAGCCAGGACATCTGAGTACCTATCTCACACACTGGACCACCAGTCACAAAGTCTGGAAAAGTTTACATTTTGGCTATCTTTACTTTGTTCTGGGAGCTGATCATGATAACCTGCAGACCTGATCAAGCCTCTGTGCCTCAGTTTCTCTCTCAGGATAAAGAGTGAATAGAGGCTGAAGGGTGAATTTCTTATTATACATAAAACACTCTGATATTATTGTATAAAGGAAGCTAAGAATATTATTTTATTTGCAAAACCCAGAAGCTAAAAAGTCAATAAACAGAAAGAATGATTTTGAGATCTCTGAGTTTTGAACAGTGGACTGGAAACCATGTAAGAGCCTTAAAAGTACAGTTCTGTGCAAATGGCATTCAGTTTTAAAGAAAAACGTAGCAAATGTTTGATGGTGCTGTTACAAAGGAGCTTGGAATACTCAGAGGAACTTGTCCCATGGTGATTTTTCACTTCTCAAAATGATGTTTAAATCCCAGTTCTCTGTTGATTCCCTTGAACAACAAACCTGGAACCTCAGCTAAGACTCTCTGTGACCAGATTCTGAACCTCTTATATCCAGGGCTTCAAGGGGTATTGCAGGTCAAGGTOTTTCCTAGGCACTTTCTACTCCCTGCATACCTCTCCTCACACTAAATTTATCCTCTAGTAGAAAATTAAGTTATTTTGGTCTAACAGCTTCAAATCTTTGAATGCTCAATAACTTATTTTGCAAGCTGCAGGCAGAAAGAGACTTTTTAAGTAAAGTCCTTTGTTTTTTCCTATTCTCTGCTTTTAGACAGGCTGTCCTCAATTTAAGCCCTGCTTTTTCTTATTGTTTCTTATATAAACTTGGTAAGTACTGTAAGAAACAGCCACTATCATACCATTGCATAATAAGGAGCACCAACTTCCCAGCTCAAAACTCAGGTCCTTATTGCCTTGTATCTTACCTCCTCTATGAGGTCAATTCACATTGTAAGCCTGTTGCTTAGTGCATCTCGTTTCCTGGTACCAGCTTCTTTAATAGAGTTCTTAGTTGCAATCAACAGAAGCTGGCTTTGGCTTTTTTATGTAGAAAAGGAACCTATTGAAAAGATACTGATTGGTTCCAATAACTGCTAGAAGTTTCTGCAAAACCATGCTTTGAAAGTGAGCAGGAAAAGAAGAGACTAGGCTGTGGCTGGGAGCACAGCCAAAATTACAAAACCAGCCCAGGGATGATGATCCTGTTCATGCACAGCCACTGTCCCCAGCACTAGGCACAGACTCTACCACTGCCTCACTGTCTCTGOTGGACTTGGAAACTTGATATTACTGTTACTGCTGCACTGTCTGCCATGAAAATGAATTCTCCAGGGTCCCTTCTTCATCCTTTCATCTCTAGCTTATAATTCAAAGTCTGGGATTGAGTGGCCAATCCTAGGTCACATGTCCATGTCCTATCTCCAAGGGGGGCTGGGAATTGAATATCTGGCATTTTCCACTTTCACTTCTTATGAATTAAGGAATTCTACAAATAATAGAAGTGGGATTCAGGTGGTAGGCAGACAAAAAAGCCTCACAATTATCCACTACGCCACCCTTGTATAACCTTACCCTCATTCACTGTCTACTCTCAAAACTGTGGAGCTACTAATGAAGATTTGTAAACCCGGGCTTATGAGCACCCATTCCTTTACTACAACTCAGATTGCTCTAGAAGCTCAGTTCCCAGCACTTGGATTTTTCCAGTAGCTGAATTCTACCTGAAGGAAGGGCAGAAACAAAGGGTGAAGAAGAGGCTATCACTTCCAAGTATCCTGCACCCCTGGGCTCAAGACCTCACTGGGGAGGGAGTCTTTTGGGCCACCCACCAAACAGCACTGGCATTATGCCTCTCACCCTAGACCATGGTTACACGTGGTAAAACAACCCCTTCTGGTGATACATTCACAACTCTCTAGTTTCCCCCAAATGGCACTATGGGGAGCGGGAGCTTGCCTTTTCCTCAGACTTAAAACAATAAGTTTTCCCCGTGTTTCCCCTCTAATGCTGTTTTCTTTTGACCAAGCATGTCTGAATTCTAGAGAAGTCAGGAGGAACACACCCATTCTCGGTTTGAAGGGACTGATGTTCTGAAGTACAACTGGGCACAGTCCCAGGCTCTTCAGGACGCTTCCTCCATTCACACAGCGGGGATGTGATTGTTACAGCGGGTGGTGTGTGCTGGCTGAGAAGCCACTGTGAATTGATTCTTCTTCTGAAGTTTATGTTTCTACTTTTTGGAAATGAATAAATTACAGCCAGTCCATCAAGGAAA (SEQ ID NO:147) >NP_003028.1 signaling lymphocytic activationmolecule isoform b precursor [Homo sapiens]MDPKGLLSLTFVLFLSLAFGASYGTGGRMMNCPKILRQLGSKVLLPLTYERINKSMNKSIHIVVTMAKSLENSVENKIVSLDPSEAGPPRYLGDRYKFYLENLTLGIRESRKEDEGWYLMTLEKNVSVQRFCLQLRLYEQVSTPEIKVLNKTQENGTCTLILGCTVEKGDHVAYSWSEKAGTHPLNPANSSHLLSLTLGPQHADNIYICTVSNPISNNSQTFSPWPGCRTDPSETKPWAVYAGLLGGVIMILIMVVILQLRRRGKTNHYQTTVEKKSLTIYAQVQKPGPLQKKLDSFPAQDPCTTIYVAATEPVPESVQETNSITVYASVTLPES (SEQ ID NO: 148) Mouse SLAM>NM_013730.4 Mus musculus signaling lymphocytic (CD150)activation molecule family member 1 (Slamf1), transcript variant 1, mRNAGAGCTTCTTCCTTGGGGGTAACAGTAAGCAGCTGTCCTGCCGAGCTGAGCTGAGCTGAGCTCACAGCTGGGGACCCTGTCTGCGATTGCTGGCTAATGGATCCCAAAGGATCCCTTTCCTGGAGAATACTTCTGTTTCTCTCCCTGGCTTTTGAGTTGAGCTACGGAACAGGTGGAGGTGTGATGGATTGCCCAGTGATTCTCCAGAAGCTGGGACAGGACACGTGGCTGCCCCTGACGAATGAACATCAGATAAATAAGAGCGTGAACAAAAGTGTCCGCATCCTCGTCACCATGGCGACGTCCCCAGGAAGCAAATCCAACAAGAAAATTGTGTCTTTTGATCTCTCTAAAGGGAGCTATCCAGATCACCTGGAGGATGGCTACCACTTTCAATCAAAAAACCTGAGCCTGAAGATCCTCGGGAACAGGCGGGAGAGTGAAGGATGGTACTTGGTGAGCGTGGAGGAGAACGTTTCTGTTCAGCAATTCTGCAAGCAGCTGAAGCTTTATGAACAGGTCTCCCCTCCAGAGATTAAAGTGCTAAACAAAACCCAGGAGAACGAGAATGGGACCTGCAGCTTGCTGTTGGCCTGCACAGTGAAGAAAGGGGACCATGTGACTTACAGCTGGAGTGATGAGGCAGGCACCCACCTGCTGAGCCGAGCCAACCGCTCCCACCTCCTGCACATCACTCTTAGCAACCAGCATCAAGACAGCATCTACAACTGCACCGCAAGCAACCCTGTCAGCAGTATCTCTAGGACCTTCAACCTATCATCGCAAGCATGCAAGCAGGAATCCTCCTCAGAATCGAGTCCATGGATGCAATATACTCTTGTACCACTGGGGGTCGTTATAATCTTCATCCTGGTTTTCACGGCAATAATAATGATGAAAAGACAAGGTAAATCAAATCACTGCCAGCCACCAGTGGAAGAAAAAAGCCTTACTATTTATGCCCAAGTACAGAAATCAGGGCCTCAAGAGAAGAAACTTCATGATGCCCTAACAGATCAGGACCCCTGCACAACCATTTATGTGGCTGCCACAGAGCCTGCCCCAGAGTCTGTCCAGGAACCAAACCCCACCACAGTTTATGCCAGTGTGACACTGCCAGAGAGCTGACCCATATACCCAGTGAAAGGACTTTTTGAAGGAGGATAGAAGAACCAAAATCCACACTGAACTGGACCCCGGGTCCCAAGTTCTCTGTGACAGAAACTGCACATCTGTAACCTTCTCCAATCAGTTCCCTGGTGACGGATCTGCACAGGCGTGCTTATGAAGTAGATGAGAAGTGAGGCTTCCTGGGCATGCAACCTGCTCTGCTGCTGACACAGATATGAAGCAGAGATCCCGTGGTACAGTGTACCATCTTTGCTGTAGCAGATAATGTGGGTTTAGGCATCTCACTCTTTGCTGGACTGGATAACAGAACTCAAAAAAAAACCAACAAGCCAAAGACATAGACTCCATCTCAGATGGCTGAGCACAAAGTATAAAAGCCATTTTGGCTCTCTGGACTTTATTCTGGAAGCTGATCCTGATCACCTCAAGGCCAAGGGCTCCATGCCTCAGTTTCTCTCTCACCCTCTAGATGAAGAGGGAACAAAGCATAAAGAGTGAAATCCTTGTTGTCTGAGATCATTCTATAAACGAACTGACATTTTATTTGCAAAACTCAAGCTAGTAATTCAGTAGACTTGAAGATGATTTTAGAGCCTCTTATGCTTCAAACAACAGAATGAAATCCATCCAATGTTCTTCAAAGTGTGGTTCTCTGATTAAGTCAAAGCAACACTGTTTGGCAATGCTGCTGTAAAGTTGCCTGGAATACTCAGAGGAACTTGTCCCAGGGAGGTTTTTTTCACTTCTTCAAAGAACTTTTGAATTTAAGTTCTCTGTTTATTCCCTTGAGCAAAACTCTGGAACCTCAAGAGTCTCTCTCCGTTGGTTCTGAGGCCATTTTATAGCCTAGGCCTCCTGTGGATCTACATGTGTATCACCCACTTCCTATCTCACTGCATACCTCTGTGTAGTAGTAAATTTAACCTCAAGTAGAAAATTAAATTATTTTGGATGATCAGTTCCAAATGATTAGATGTTTAGTCTCTTATAATAGGATGTAGGTAGAGTCTATATAAAGTCCTATATTCTTCACGTTGTCTGTCCTCAGAGAGACCATCTTTCAACCTATCTTCCTTCTTGCACAACTTTGGCAAATACTTTAAAAATAACCATTGTGGAGATGGGGAGAGGTCTAAATGGATAATAGTACTTGCTTTGCAAACATGAAGATCTGGGTTCAAACTCCCAGTGTCCATGTAAAAAGATAAGTGTGGTTGAGTGTGCCAGTAACATAGACACAGATAGGTCCTGAGACTTTGCTCCCTAGCCTTCCCAGCCAGGCATAAATGTCAAGTCCCCTGAGAGTGACAGAGGAAGATACTCCCCCCACACACACACACATACACGCACAGTGATACACATATACATGCATACAAAAAAAAAACTTATTGTAACAAAGAACACCAACTGCCTGGCTCAAAACTCTCATGTCCCATTACTCTGTACCTTTCTGTATTTAGATAATTTACAGTGTGAGTTCTGOTGTTCCATGTATCCTATTTGTGTTACTAACTTATGTCAAAGTATTTCTAATTATAATCAACAAAAGCTAACTTTG (SEQ ID NO:149) >NP_038758.2 signaling lymphocytic activationmolecule isoform 1 precursor [Mus musculus]MDPKGSLSWRILLFLSLAFELSYGTGGGVMDCPVILQKLGQDTWLPLTNEHQINKSVNKSVRILVTMATSPGSKSNKKIVSFDLSKGSYPDHLEDGYHFQSKNLSLKILGNRRESEGWYLVSVEENVSVQQFCKQLKLYEQVSPPEIKVLNKTQENENGTCSLLLACTVKKGDHVTYSWSDEAGTHLLSRANRSHLLHITLSNQHQDSIYNCTASNPVSSISRTFNLSSQACKQESSSESSPWMQYTLVPLGVVIIFILVFTAIIMMKRQGKSNHCQPPVEEKSLTIYAQVQKSGPQEKKLHDALTDQDPCTTIYVAATEPAPESVQEPNPTTVYASVTLPES (SEQ ID NO: 150) Human CD40>NM_001250.6 Homo sapiens CD40 molecule (CD40),transcript variant 1, mRNAAGTGGTCCTGCCGCCTGGTCTCACCTCGCTATGGTTCGTCTGCCTCTGCAGTGCGTCCTCTGGGGCTGCTTGCTGACCGCTGTCCATCCAGAACCACCCACTGCATGCAGAGAAAAACAGTACCTAATAAACAGTCAGTGOTGTTCTTTGTGCCAGCCAGGACAGAAACTGGTGAGTGACTGCACAGAGTTCACTGAAACGGAATGCCTTCCTTGCGGTGAAAGCGAATTCCTAGACACCTGGAACAGAGAGACACACTGCCACCAGCACAAATACTGCGACCCCAACCTAGGGCTTCGGGTCCAGCAGAAGGGCACCTCAGAAACAGACACCATCTGCACCTGTGAAGAAGGCTGGCACTGTACGAGTGAGGCCTGTGAGAGCTGTGTCCTGCACCGCTCATGCTCGCCCGGCTTTGGGGTCAAGCAGATTGCTACAGGGGTTTCTGATACCATCTGCGAGCCCTGCCCAGTCGGCTTCTTCTCCAATGTGTCATCTGCTTTCGAAAAATGTCACCCTTGGACAAGCTGTGAGACCAAAGACCTGGTTGTGCAACAGGCAGGCACAAACAAGACTGATGTTGTCTGTGGTCCCCAGGATCGGCTGAGAGCCCTGGTGGTGATCCCCATCATCTTCGGGATCCTGTTTGCCATCCTCTTGGTGCTGGTCTTTATCAAAAAGGTGGCCAAGAAGCCAACCAATAAGGCCCCCCACCCCAAGCAGGAACCCCAGGAGATCAATTTTCCCGACGATCTTCCTGGCTCCAACACTGCTGCTCCAGTGCAGGAGACTTTACATGGATGCCAACCGGTCACCCAGGAGGATGGCAAAGAGAGTCGCATCTCAGTGCAGGAGAGACAGTGAGGCTGCACCCACCCAGGAGTGTGGCCACGTGGGCAAACAGGCAGTTGGCCAGAGAGCCTGGTGCTGCTGCTGCTGTGGCGTGAGGGTGAGGGGCTGGCACTGACTGGGCATAGCTCCCCGCTTCTGCCTGCACCCCTGCAGTTTGAGACAGGAGACCTGGCACTGGATGCAGAAACAGTTCACCTTGAAGAACCTCTCACTTCACCCTGGAGCCCATCCAGTCTCCCAACTTGTATTAAAGACAGAGGCAGAAGTTTGGTGGTGGTGGTGTTGGGGTATGGTTTAGTAATATCCACCAGACCTTCCGATCCAGCAGTTTGGTGCCCAGAGAGGCATCATGGTGGCTTCCCTGCGCCCAGGAAGCCATATACACAGATGCCCATTGCAGCATTGTTTGTGATAGTGAACAACTGGAAGCTGCTTAACTGTCCATCAGCAGGAGACTGGCTAAATAAAATTAGAATATATTTATACAACAGAATCTCAAAAACACTGTTGAGTAAGGAAAAAAAGGCATGCTGCTGAATGATGGGTATGGAACTTTTTAAAAAAGTACATGCTTTTATGTATGTATATTGCCTATGGATATATGTATAAATACAATATGCATCATATATTGATATAACAAGGGTTCTGGAAGGGTACACAGAAAACCCACAGCTCGAAGAGTGGTGACGTCTGGGGTGGGGAAGAAGGGTCTGGGGGAGGGTTGGTTAAAGGGAGATTTGGCTTTCCCATAATGCTTCATCATTTTTCCCAAAAGGAGAGTGAATTCACATAATGCTTATGTAATTAAAAAATCATCAAACATGTAAAAA (SEQ ID NO:151) >NP_001241.1 tumor necrosis factor receptorsuperfamily member 5 isoform 1 precursor [Homo sapiens]MVRLPLQCVLWGCLLTAVHPEPPTACREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTCEEGWHCTSEACESCVLHRSCSPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEKCHPWTSCETKDLVVQQAGTNKTDVVCGPQDRLRALVVIPIIFGILFAILLVLVFIKKVAKKPTNKAPHPKQEPQEINFPDDLPGSNTAAPVQETLHGCQPVTQEDGKESRISVQERQ (SEQ ID NO: 152) Mouse CD40>NM_170703.2 Mus musculus CD40 antigen (Cd40),transcript variant 2, mRNAAGCAGGGACTTTGGAGTGACTTGTGGCTTCAGCAGGAGCCCTGTGATTTGGCTCTTCTGATCTCGCCCTGCGATGGTGTCTTTGCCTCGGCTGTGCGCGCTATGGGGCTGCTTGTTGACAGCGGTCCATCTAGGGCAGTGTGTTACGTGCAGTGACAAACAGTACCTCCACGATGGCCAGTGCTGTGATTTGTGCCAGCCAGGAAGCCGACTGACAAGCCACTGCACAGCTCTTGAGAAGACCCAATGCCACCCATGTGACTCAGGCGAATTCTCAGCCCAGTGGAACAGGGAGATTCGCTGTCACCAGCACAGACACTGTGAACCCAATCAAGGGCTTCGGGTTAAGAAGGAGGGCACCGCAGAATCAGACACTGTCTGTACCTGTAAGGAAGGACAACACTGCACCAGCAAGGATTGCGAGGCATGTGCTCAGCACACGCCCTGTATCCCTGGCTTTGGAGTTATGGAGATGGCCACTGAGACCACTGATACCGTCTGTCATCCCTGCCCAGTCGGCTTCTTCTCCAATCAGTCATCACTTTTCGAAAAGTGTTATCCCTGGACAAGGTTTAAAGTCCCGGATGCGAGCCCTGCTGGTCATTCCTGTCGTGATGGGCATCCTCATCACCATTTTCGGGGTGTTTCTCTATATCAAAAAGGTGGTCAAGAAACCAAAGGATAATGAGATCTTACCCCCTGCGGCTCGACGGCAAGATCCCCAGGAGATGGAAGATTATCCCGGTCATAACACCGCTGCTCCAGTGCAGGAGACGCTGCACGGGTGTCAGCCTGTCACACAGGAGGATGGTAAAGAGAGTCGCATCTCAGTGCAGGAGCGGCAGGTGACAGACAGCATAGCCTTGAGGCCCCTGGTCTGAACCCTGGAACTGCTTTGGAGGCGATGGCTCGGCTCGGGAGCAGGGGCCTGGCTCTGAGGACTGCTTGCTGACCTTTGAAGTTTGAGATGAGCCAAGACAGAGCCCAGTGCAGCTAACTCTCATGCCTGCCCCCTATCATTTCTCAACTTGCTTTTTAAGGATGGAGGGAGAGCTCGGGCATCGGGGGTCCACAGTGATACCTACCAAGTGCAGCAGTGCAGGACCCAGAGTCGTCTTGCTGCGGCGTTCACTGTAAGGAGTCATGGACACAGGAGTCCGTGGCCCACAGCTTGTGCTGCTAGAGGGCACCTGGTTGCCCATCAGCAGGGTACTGGCTAAATAAATCTGTAATTATTTATACAATGACATCTCAGAAACTCTAGCAGGTGGGGCAGAAAACAGGTAGTAGAATGATGGGTAGAGAAATAGCTTTTAAAACACATTCCAAGGCAGGTAAGATGGCTTTTGTGAGTAAAGGAGCTTGCTGCCCAAACCCGGTTACCTGATTTTGATCCCTGGGACTTCATGGTAAAAGGGAGAGAACCAAATCCAGAGGGTTGTCATTTGACCTCCATGTGTGCTCTGTGGTAATGTACCCCGTGTGTGCACATGTGCACATATCCTAAAATGGATGTGGTGGTGTATTGTAGAAATTATTTAATCCCGCCCTGGGGTTTCTACCTGTGTGTTACCATTTAGTTCTTGAATAAAAGACACACTCAACCTTTATATTTACAATAA (SEQ ID NO: 153) >NP_733804.1 tumor necrosis factor receptorsuperfamily member 5 isoform 2 precursor [Mus musculus]MVSLPRLCALWGCLLTAVHLGQCVTCSDKQYLHDGQCCDLCQPGSRLTSHCTALEKTQCHPCDSGEFSAQWNREIRCHQHRHCEPNQGLRVKKEGTAESDTVCTCKEGQHCTSKDCEACAQHTPCIPGFGVMEMATETTDTVCHPCPVGFFSNQSSLFEKCYPWTRFKVPDASPAGHSCRDGHPHHHFRGVSLYQKGGQETKG (SEQ ID NO: 154) Human CD28>NM_006139.4 Homo sapiens CD28 molecule (CD28),transcript variant 1, mRNAACACTTCGGGTTCCTCGGGGAGGAGGGGCTGGAACCCTAGCCCATCGTCAGGACAAAGATGCTCAGGCTGCTCTTGGCTCTCAACTTATTCCCTTCAATTCAAGTAACAGGAAACAAGATTTTGGTGAAGCAGTCGCCCATGCTTGTAGCGTACGACAATGCGGTCAACCTTAGCTGCAAGTATTCCTACAATCTCTTCTCAAGGGAGTTCCGGGCATCCCTTCACAAAGGACTGGATAGTGCTGTGGAAGTCTGTGTTGTATATGGGAATTACTCCCAGCAGCTTCAGGTTTACTCAAAAACGGGGTTCAACTGTGATGGGAAATTGGGCAATGAATCAGTGACATTCTACCTCCAGAATTTGTATGTTAACCAAACAGATATTTACTTCTGCAAAATTGAAGTTATGTATCCTCCTCCTTACCTAGACAATGAGAAGAGCAATGGAACCATTATCCATGTGAAAGGGAAACACCTTTGTCCAAGTCCCCTATTTCCCGGACCTTCTAAGCCCTTTTGGGTGCTGGTGGTGGTTGGTGGAGTCCTGGCTTGCTATAGCTTGCTAGTAACAGTGGCCTTTATTATTTTCTGGGTGAGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTCCTGACACGGACGCCTATCCAGAAGCCAGCCGGCTGGCAGCCCCCATCTGCTCAATATCACTGCTCTGGATAGGAAATGACCGCCATCTCCAGCCGGCCACCTCAGGCCCCTGTTGGGCCACCAATGCCAATTTTTCTCGAGTGACTAGACCAAATATCAAGATCATTTTGAGACTCTGAAATGAAGTAAAAGAGATTTCCTGTGACAGGCCAAGTCTTACAGTGCCATGGCCCACATTCCAACTTACCATGTACTTAGTGACTTGACTGAGAAGTTAGGGTAGAAAACAAAAAGGGAGTGGATTCTGGGAGCCTCTTCCCTTTCTCACTCACCTGCACATCTCAGTCAAGCAAAGTGTGGTATCCACAGACATTTTAGTTGCAGAAGAAAGGCTAGGAAATCATTCCTTTTGGTTAAATGGGTGTTTAATCTTTTGGTTAGTGGGTTAAACGGGGTAAGTTAGAGTAGGGGGAGGGATAGGAAGACATATTTAAAAACCATTAAAACACTGTCTCCCACTCATGAAATGAGCCACGTAGTTCCTATTTAATGCTGTTTTCCTTTAGTTTAGAAATACATAGACATTGTCTTTTATGAATTCTGATCATATTTAGTCATTTTGACCAAATGAGGGATTTGGTCAAATGAGGGATTCCCTCAAAGCAATATCAGGTAAACCAAGTTGCTTTCCTCACTCCCTGTCATGAGACTTCAGTGTTAATGTTCACAATATACTTTCGAAAGAATAAAATAGTTCTCCTACATGAAGAAAGAATATGTCAGGAAATAAGGTCACTTTATGTCAAAATTATTTGAGTACTATGGGACCTGGCGCAGTGGCTCATGCTTGTAATCCCAGCACTTTGGGAGGCCGAGGTGGGCAGATCACTTGAGATCAGGACCAGCCTGGTCAAGATGGTGAAACTCCGTCTGTACTAAAAATACAAAATTTAGCTTGGCCTGGTGGCAGGCACCTGTAATCCCAGCTGCCCAAGAGGCTGAGGCATGAGAATCGCTTGAACCTGGCAGGCGGAGGTTGCAGTGAGCCGAGATAGTGCCACAGCTCTCCAGCCTGGGCGACAGAGTGAGACTCCATCTCAAACAACAACAACAACAACAACAACAACAACAAACCACAAAATTATTTGAGTACTGTGAAGGATTATTTGTCTAACAGTTCATTCCAATCAGACCAGGTAGGAGCTTTCCTGTTTCATATGTTTCAGGGTTGCACAGTTGGTCTCTTTAATGTCGGTGTGGAGATCCAAAGTGGGTTGTGGAAAGAGCGTCCATAGGAGAAGTGAGAATACTGTGAAAAAGGGATGTTAGCATTCATTAGAGTATGAGGATGAGTCCCAAGAAGGTTCTTTGGAAGGAGGACGAATAGAATGGAGTAATGAAATTCTTGCCATGTGCTGAGGAGATAGCCAGCATTAGGTGACAATCTTCCAGAAGTGGTCAGGCAGAAGGTGCCCTGGTGAGAGCTCCTTTACAGGGACTTTATGTGGTTTAGGGCTCAGAGCTCCAAAACTCTGGGCTCAGCTGCTCCTGTACCTTGGAGGTCCATTCACATGGGAAAGTATTTTGGAATGTGTCTTTTGAAGAGAGCATCAGAGTTCTTAAGGGACTGGGTAAGGCCTGACCCTGAAATGACCATGGATATTTTTCTACCTACAGTTTGAGTCAACTAGAATATGCCTGGGGACCTTGAAGAATGGCCCTTCAGTGGCCCTCACCATTTGTTCATGCTTCAGTTAATTCAGGTGTTGAAGGAGCTTAGGTTTTAGAGGCACGTAGACTTGGTTCAAGTCTCGTTAGTAGTTGAATAGCCTCAGGCAAGTCACTGCCCACCTAAGATGATGGTTCTTCAACTATAAAATGGAGATAATGGTTACAAATGTCTCTTCCTATAGTATAATCTCCATAAGGGCATGGCCCAAGTCTGTCTTTGACTCTGCCTATCCCTGACATTTAGTAGCATGCCCGACATACAATGTTAGCTATTGGTATTATTGCCATATAGATAAATTATGTATAAAAATTAAACTGGGCAATAGCCTAAGAAGGGGGGAATATTGTAACACAAATTTAAACCCACTACGCAGGGATGAGGTGCTATAATATGAGGACCTTTTAACTTCCATCATTTTCCTGTTTCTTGAAATAGTTTATCTTGTAATGAAATATAAGGCACCTCCCACTTTTATGTATAGAAAGAGGTCTTTTAATTTTTTTTTAATGTGAGAAGGAAGGGAGGAGTAGGAATCTTGAGATTCCAGATCGAAAATACTGTACTTTGGTTGATTTTTAAGTGGGCTTCCATTCCATGGATTTAATCAGTCCCAAGAAGATCAAACTCAGCAGTACTTGGGTGCTGAAGAACTGTTGGATTTACCCTGGCACGTGTGCCACTTGCCAGCTTCTTGGGCACACAGAGTTCTTCAATCCAAGTTATCAGATTGTATTTGAAAATGACAGAGCTGGAGAGTTTTTTGAAATGGCAGTGGCAAATAAATAAATACTTTTTTTTAAATGGAAAGACTTGATCTATGGTAATAAATGATTTTGTTTTCTGACTGGAAAAATAGGCCTACTAAAGATGAATCACACTTGAGATGTTTCTTACTCACTCTGCACAGAAACAAAGAAGAAATGTTATACAGGGAAGTCCGTTTTCACTATTAGTATGAACCAAGAAATGGTTCAAAAACAGTGGTAGGAGCAATGCTTTCATAGTTTCAGATATGGTAGTTATGAAGAAAACAATGTCATTTGCTGCTATTATTGTAAGAGTCTTATAATTAATGGTACTCCTATAATTTTTGATTGTGAGCTCACCTATTTGGGTTAAGCATGCCAATTTAAAGAGACCAAGTGTATGTACATTATGTTCTACATATTCAGTGATAAAATTACTAAACTACTATATGTCTGCTTTAAATTTGTACTTTAATATTGTCTTTTGGTATTAAGAAAGATATGCTTTCAGAATAGATATGCTTCGCTTTGGCAAGGAATTTGGATAGAACTTGCTATTTAAAAGAGGTGTGGGGTAAATCCTTGTATAAATCTCCAGTTTAGCCTTTTTTGAAAAAGCTAGACTTTCAAATACTAATTTCACTTCAAGCAGGGTACGTTTCTGGTTTGTTTGCTTGACTTCAGTCACAATTTCTTATCAGACCAATGGCTGACCTCTTTGAGATGTCAGGCTAGGCTTACCTATGTGTTCTGTGTCATGTGAATGCTGAGAAGTTTGACAGAGATCCAACTTCAGCCTTGACCCCATCAGTCCCTCGGGTTAACTAACTGAGCCACCGGTCCTCATGGCTATTTTAATGAGGGTATTGATGGTTAAATGCATGTCTGATCCCTTATCCCAGCCATTTGCACTGCCAGCTGGGAACTATACCAGACCTGGATACTGATCCCAAAGTGTTAAATTCAACTACATGCTGGAGATTAGAGATGGTGCCAATAAAGGACCCAGAACCAGGATCTTGATTGCTATAGACTTATTAATAATCCAGGTCAAAGAGAGTGACACACACTCTCTCAAGACCTGGGGTGAGGGAGTCTGTGTTATCTGCAAGGCCATTTGAGGCTCAGAAAGTCTCTCTTTCCTATAGATATATGCATACTTTCTGACATATAGGAATGTATCAGGAATACTCAACCATCACAGGCATGTTCCTACCTCAGGGCCTTTACATGTCCTGTTTACTCTGTCTAGAATGTCCTTCTGTAGATGACCTGGCTTGCCTCGTCACCCTTCAGGTCCTTGCTCAAGTGTCATCTTCTCCCCTAGTTAAACTACCCCACACCCTGTCTGCTTTCCTTGCTTATTTTTCTCCATAGCATTTTACCATCTCTTACATTAGACATTTTTCTTATTTATTTGTAGTTTATAAGCTTCATGAGGCAAGTAACTTTGCTTTGTTTCTTGCTGTATCTCCAGTGCCCAGAGCAGTGCCTGGTATATAATAAATATTTATTGACTGAGTGAA (SEQ ID NO: 155) >NP_006130.1 T-cell-specific surface glycoproteinCD28 isoform 1 precursor [Homo sapiens]MLRLLLALNLFPSIQVTGNKILVKQSPMLVAYDNAVNLSCKYSYNLFSREFRASLHKGLDSAVEVCVVYGNYSQQLQVYSKTGFNCDGKLGNESVTFYLQNLYVNQTDIYFCKIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS (SEQ ID NO: 156) Mouse CD28>NM_007642.4 Mus musculus CD28 antigen (Cd28), mRNAAGACCTTGGCAGATGTGACTTCAGTTCACACCACACTCTGCCTTGCTCACAGAGGAGGGGCTGCAGCCCTGGCCCTCATCAGAACAATGACACTCAGGCTGCTGTTCTTGGCTCTCAACTTCTTCTCAGTTCAAGTAACAGAAAACAAGATTTTGGTAAAGCAGTCGCCCCTGCTTGTGGTAGATAGCAACGAGGTCAGCCTCAGCTGCAGGTATTCCTACAACCTTCTCGCAAAGGAATTCCGGGCATCCCTGTACAAGGGCGTGAACAGCGACGTGGAAGTCTGTGTCGGGAATGGGAATTTTACCTATCAGCCCCAGTTTCGCTCGAATGCCGAGTTCAACTGCGACGGGGATTTCGACAACGAAACAGTGACGTTCCGTCTCTGGAATCTGCACGTCAATCACACAGATATTTACTTCTGCAAAATTGAGTTCATGTACCCTCCGCCTTACCTAGACAACGAGAGGAGCAATGGAACTATTATTCACATAAAAGAGAAACATCTTTGTCATACTCAGTCATCTCCTAAGCTGTTTTGGGCACTGGTCGTGGTTGCTGGAGTCCTGTTTTGTTATGGCTTGCTAGTGACAGTGGCTCTTTGTGTTATCTGGACAAATAGTAGAAGGAACAGACTCCTTCAAAGTGACTACATGAACATGACTCCCCGGAGGCCTGGGCTCACTCGAAAGCCTTACCAGCCCTACGCCCCTGCCAGAGACTTTGCAGCGTACCGCCCCTGACAGGGACCCCTATCCAGAAGCCCGCCGGCTGGTACCCGTCTACCTGCTCATCATCACTGCTCTGGATAGGAAAGGACAGCCTCATCTTCAGCCGGCCACTTTGGACCTCTACTGGGCCACCAATGCCAACTATTTTAGAGTGTCTAGATCTAACATCATGATCATCTTGAGACTCTGGAATGAATGACAGAAGCTTCTATGGCAGGATAAAGTCTGTGTGGCTTGACCCAAACTCAAGCTTAATACATTTATTGACTTGATTGGGGAAGTTAGAGTAGAGCAATCAAAAAGATCATTCATTCAGCCTTGGGAAGTCAATTTGCAGGCTCCTGGATGAGCCCTGCCCCGTTTTCACTTGCCAGCACATTTCAGTCATGTGGTGTGATAGCCAAAGATGTTTTGGACAGAGAAGAAAGGATAGAAAAACCTTCTCTTTGGCTAAGTTGGTGTTTGGGGTGGGGATAGGTTAGAGTATAGTACTTAACTATTTGAAAAATAATGAAAACACTTTTTTCACTCATGAAATGAGCCACTTAGCTCCTAAATAGTGTTTTCCTGTTAGTTTAGAAAGTTGTGGACATATTTTTTTAATGATTTCTGACCATTTTTAATCACATTGACTCATGGAATGGCCTCAAAGCACCCCCCAGTGCTTCTTTCCTCATTCCCGGTCATGGGAACTCAGTATTATTAATAGTCACAACATGATTTCAGAACTAGATAGCCCTCCCACACCAAGAAGAATGTGAGAGGAAGTAAGGTCACTTTATGTAAAAAAAAAAAAAAACAAACGCGTACACATATGTATGTATACATACATACCTATGTGCACACACACACACATATACATACACACAAAATGCTATGAAGAGTTATCTGTTTAGTAGCCTGTTATAGTCAAATCATTTTAAGTTTCAACTTCTTACAGTTGGGCCACTTGTTGTCCTTTGTGGATGGATATCTGAAATTGTGTCTATATATTGCTAGTCATGATACTGTGAACAAAAAGGGTAGTGTTAGTATTTGTCAGGGTGGTAAGGATGCATTCCAGGAAGCTTCCTCTGAGGAAGGGAATGAGGTCATTCTTGCCATGTATGAAAGACATAGATGTTTTCCAGAAGGCACCATTGGGAGCCCCAGTATAAGTTCCTTTAGACTCTACAGTTTAGAGGGATTTTATATGTCCTAGGACTCAGGACTCCAGAACTTTGTGGGCTCAGCTGCTTCATACCATGGGGATACATTGACATGAACAATTATTTTGGAATGTGTCTTTAGGGACGACATCAAAGTTCTCAAGTACCTACAAGACCTGATACTGGAATGAAGGTGGACTTTCTTTTTTGCTTCCAGTTCGGATCAACTGGAATGTATCTGGGGACCTTGAAGAACGGCTGTCCAGCTGTCTTCACCATTTGTATAGTGCTTTGAATTATTCAGAGGTTTTAAAGTCAGGAAGACCTGGTTTAAAAAACATTTCATTATGAGTTAAATGGCCTCAGGCAAGTCACTGTTCATCCAAGTCTATGACTCCTCAACTGTAAGATGGCCACACTGAAACTTGCTAAGATCCTCTGGCCTCTGCCTCCCAAGAGTTGGGATTTCAGGAGTGCACAATCATGACCCAAACTCGTGATAATCTCTCAGCTTCAATAACTTTCCAGCTAATTGGAATATCCTGTAATCAAACATGAGGCATTTCCCCTCCCCCCACTGTTTTTGTGTATAAAGAGATCTTTAAACTTTTTTTTTAATATGAGGGGTAAGAAAAGATAGGAATCTTTTAATTCTAGACAGAAGATATTGTGCTTTGGTTTTTTTTTTTTTTAATGGCTTCTATTCTGTGCTTTTAATTAAACCAGAGAAGGCCAAGATTAGCCCTACTTGTGTGATAAAAGAATGCTGGCCCTTGTGATTGCAGTCAGCCTCTTGACACATAGAGTTCTTGAATCTAAGTTATAAAATTATATTTGAAAATGACAGAGCTGGAGAATTTATAGAAAGGGTCATAGCAAATAACAAACCATTTTTTTTTAAACGGAAAGATTTGGTCTTTGGCAATCAATAACTTTGTTTTCTAACTGGAAAAGGAGGTTTACTGGAGATGAATCACACCTGAAAGTTTTCATACCTCCTCTGAACACAACCGAAACATAGGTGTCCAAAGCCTTTCGCTCTCGGTATGAACCAACAGGCGGGTTAAAAACACTGGGTCAGAGTAAAGCTTTTGCAGTTTCAGATGTAGTGTGTATGAAGAAAACTATGTCACTTGCTGCTATTATTGTAAGAGTCTAAGAACTAAAGGTGTGCCTGTAATTTCTAATTATGAGCTCACCTATTTGGTACCGAGCATGCCAATTTTAAAGAGACCCGGTGTACCTTATAGCTACATCCAATGATAAAATTACCACACTAGCACATGCCTGTGTTTAAACTCGTGCTTTAATGTTTTTCTTAGGGCAGGTATGCACCCCCTTTGCAGTGAGTTGGGAGAGATTTTGAAAAAGTGTATGACAAACATTTTTAACACCTTTGGTTTCCTCTCTCTGTGTCTCTTTGTCTCTGTCTCTCTCTTTCTCTCCTGTGCATATGTCTCCCCTCCCTCACTTCTCTGTCTCTTCCTCTCTCCCTCTCTCTGTCTTTCTCTGTGTGTCTCTCTGTCTCTGTGTATCTCTCTGTCTGTCTCTTTCTCTGCAGATTTTCAAAACGTTGTTTTTCTATGGAAGAAATACAAGCTGTGGTTGGTTTGCTACGAGTCAGTAGCAGTTTATCAGTAGGCCAATGTTTTATCTCTTGGAGATTTCAGTCTGGGTTTACCCAATGTATTCTCTGTAATGTGACTGCTGGGGACAGATATAACTTGATTGAGCCTTCAAATCATTTAGGTCTTCAATCATTTAGTCAACGGAGTGAGCCACTAATCTGCAATGGCTATTTTAATATGCATACTGATGGTCAAATGGATGTCTGATCTCTCATCCCAGCTTTCTGTACTACCATATGGGAACTATATGTAACTTGTATACTTACCTGAATATGTTAAATTCAACTACATGGTAAGATGGACCAGAAATTGCAATGTTCATGTCCATATAGCCACCATTAACCCAAGTTAAGCACAGTAGTGTGGGTTCTCTCAGGACTTGTGAATGAGTTTATGCTCTCTACAAAGACAGGTGAAGCTTAAATCTCTCTTGCACTGCTATGTTTATGCAAATATCAAGATTGTTTCTGTACCAGGGACTTAACACATTCTATTCATACTATTTTCCCTGTCTACAATGTTATTTCATAGATATCTACTTGGTTTGCTCTTACTTCCTTGACATATTTGCCCAAATGCCACCTTCAACTGTAGTTAATTACCTGTACAACCTGTCTCCATGCCTTGTTTTATTTTCTCTATAACTCTACTAATAGGTATTTTTCTTATTTATTGGTTTATTGCCTGTTTTTTTTCCTAAATCTACACCGGATCTCCAAAGGGAAAGAACTCCATTTGCTTTGATTTTATTGCTGTATCCCCAGTGCCTAGAATAATGCTTAGCCTGCAATAAATATTTATTCATTGACT (SEQ ID NO: 157) >NP_031668.3 T-cell-specific surface glycoproteinCD28 precursor [Mus musculus]MTLRLLFLALNFFSVQVTENKILVKQSPLLVVDSNEVSLSCRYSYNLLAKEFRASLYKGVNSDVEVCVGNGNFTYQPQFRSNAEFNCDGDFDNETVTFRLWNLHVNHTDIYFCKIEFMYPPPYLDNERSNGTIIHIKEKHLCHTQSSPKLFWALVVVAGVLFCYGLLVTVALCVIWTNSRRNRLLQSDYMNMTPRRPGLTRKPYQPYAPARDFAAYRP (SEQ ID NO: 158) Human>NM_144615.2 Homo sapiens transmembrane and CD28Himmunoglobulin domain containing 2 (TMIGD2), transcript variant 1, mRNAGGAAGTCTGTCAACTGGGAGGGGGAGAGGGGGGTGATGGGCCAGGAATGGGGTCCCCGGGCATGGTGCTGGGCCTCCTGGTGCAGATCTGGGCCCTGCAAGAAGCCTCAAGCCTGAGCGTGCAGCAGGGGCCCAACTTGCTGCAGGTGAGGCAGGGCAGTCAGGCGACCCTGGTCTGCCAGGTGGACCAGGCCACAGCCTGGGAACGGCTCCGTGTTAAGTGGACAAAGGATGGGGCCATCCTGTGTCAACCGTACATCACCAACGGCAGCCTCAGCCTGGGGGTCTGCGGGCCCCAGGGACGGCTCTCCTGGCAGGCACCCAGCCATCTCACCCTGCAGCTGGACCCTGTGAGCCTCAACCACAGCGGGGCGTACGTGTGCTGGGCGGCCGTAGAGATTCCTGAGTTGGAGGAGGCTGAGGGCAACATAACAAGGCTCTTTGTGGACCCAGATGACCCCACACAGAACAGAAACCGGATCGCAAGCTTCCCAGGATTCCTCTTCGTGCTGCTGGGGGTGGGAAGCATGGGTGTGGCTGCGATCGTGTGGGGTGCCTGGTTCTGGGGCCGCCGCAGCTGCCAGCAAAGGGACTCAGGTAACAGCCCAGGAAATGCATTCTACAGCAACGTCCTATACCGGCCCCGGGGGGCCCCAAAGAAGAGTGAGGACTGCTCTGGAGAGGGGAAGGACCAGAGGGGCCAGAGCATTTATTCAACCTCCTTCCCGCAACCGGCCCCCCGCCAGCCGCACCTGGCGTCAAGACCCTGCCCCAGCCCGAGACCCTGCCCCAGCCCCAGGCCCGGCCACCCCGTCTCTATGGTCAGGGTCTCTCCTAGACCAAGCCCCACCCAGCAGCCGAGGCCAAAAGGGTTCCCCAAAGTGGGAGAGGAGTGAGAGATCCCAGGAGACCTCAACAGGACCCCACCCATAGGTACACACAAAAAAGGGGGGATCGAGGCCAGACACGGTGGCTCACGCCTGTAATCCCAGCAGTTTGGGAAGCCGAGGCGGGTGGAACACTTGAGGTCAGGGGTTTGAGACCAGCCTGGCTTGAACCTGGGAGGCGGAGGTTGCAGTGAGCCGAGATTGCGCCACTGCACTCCAGCCTGGGCGACAGAGTGAGACTCCGTCTCAAAAAAAACAAAAAGCAGGAGGATTGGGAGCCTGTCAGCCCCATCCTGAGACCCCGTCCTCATTTCTGTAATGATGGATCTCGCTCCCACTTTCCCCCAAGAACCTAATAAAGGCTTGTGAAGAAAAAGCAAAAAAAAAAAAAAAAAA (SEQ ID NO: 159) >NP_653216.2 transmembrane and immunoglobulin domain-containing protein 2 isoform 1 precursor [Homo sapiens]MGSPGMVLGLLVQIWALQEASSLSVQQGPNLLQVRQGSQATLVCQVDQATAWERLRVKWTKDGAILCQPYITNGSLSLGVCGPQGRLSWQAPSHLTLQLDPVSLNHSGAYVCWAAVEIPELEEAEGNITRLFVDPDDPTQNRNRIASFPGFLFVLLGVGSMGVAAIVWGAWFWGRRSCQQRDSGNSPGNAFYSNVLYRPRGAPKKSEDCSGEGKDQRGQSIYSTSFPQPAPRQPHLASRPCPSPRPCPSPRPGHPVSMVRVSPRPSPTQQPRPKGFPKVGEE (SEQ ID NO: 160) Human CD2>NM_001328609.2 Homo sapiens CD2 molecule (CD2),transcript variant 1, mRNAAGTCTCACTTCAGTTCCTTTTGCATGAAGAGCTCAGAATCAAAAGAGGAAACCAACCCCTAAGATGAGCTTTCCATGTAAATTTGTAGCCAGCTTCCTTCTGATTTTCAATGTTTCTTCCAAAGGTGCAGTCTCCAAAGAGATTACGAATGCCTTGGAAACCTGGGGTGCCTTGGGTCAGGACATCAACTTGGACATTCCTAGTTTTCAAATGAGTGATGATATTGACGATATAAAATGGGAAAAAACTTCAGACAAGAAAAAGATTGCACAATTCAGAAAAGAGAAAGAGACTTTCAAGGAAAAAGATACATATAAGCTATTTAAAAATGGAACTCTGAAAATTAAGCATCTGAAGACCGATGATCAGGATATCTACAAGGTATCAATATATGATACAAAAGGAAAAAATGTGTTGGAAAAAATATTTGATTTGAAGATTCAAGAGAGGGTCTCAAAACCAAAGATCTCCTGGACTTGTATCAACACAACCCTGACCTGTGAGGTAATGAATGGAACTGACCCCGAATTAAACCTGTATCAAGATGGGAAACATCTAAAACTTTCTCAGAGGGTCATCACACACAAGTGGACCACCAGCCTGAGTGCAAAATTCAAGTGCACAGCAGGGAACAAAGTCAGCAAGGAATCCAGTGTCGAGCCTGTCAGCTGTCCAGGAGGCAGCATCCTTGGCCAGAGTAATGGGCTCTCTGCCTGGACCCCTCCCAGCCATCCCACTTCTCTTCCTTTTGCAGAGAAAGGTCTGGACATCTATCTCATCATTGGCATATGTGGAGGAGGCAGCCTCTTGATGGTCTTTGTGGCACTGCTCGTTTTCTATATCACCAAAAGGAAAAAACAGAGGAGTCGGAGAAATGATGAGGAGCTGGAGACAAGAGCCCACAGAGTAGCTACTGAAGAAAGGGGCCGGAAGCCCCACCAAATTCCAGCTTCAACCCCTCAGAATCCAGCAACTTCCCAACATCCTCCTCCACCACCTGGTCATCGTTCCCAGGCACCTAGTCATCGTCCCCCGCCTCCTGGACACCGTGTTCAGCACCAGCCTCAGAAGAGGCCTCCTGCTCCGTCGGGCACACAAGTTCACCAGCAGAAAGGCCCGCCCCTCCCCAGACCTCGAGTTCAGCCAAAACCTCCCCATGGGGCAGCAGAAAACTCATTGTCCCCTTCCTCTAATTAAAAAAGATAGAAACTGTCTTTTTCAATAAAAAGCACTGTGGATTTCTGCCCTCCTGATGTGCATATCCGTACTTCCATGAGGTGTTTTCTGTGTGCAGAACATTGTCACCTCCTGAGGCTGTGGGCCACAGCCACCTCTGCATCTTCGAACTCAGCCATGTGGTCAACATCTGGAGTTTTTGGTCTCCTCAGAGAGCTCCATCACACCAGTAAGGAGAAGCAATATAAGTGTGATTGCAAGAATGGTAGAGGACCGAGCACAGAAATCTTAGAGATTTCTTGTCCCCTCTCAGGTCATGTGTAGATGCGATAAATCAAGTGATTGGTGTGCCTGGGTCTCACTACAAGCAGCCTATCTGCTTAAGAGACTCTGGAGTTTCTTATGTGCCCTGGTGGACACTTGCCCACCATCCTGTGAGTAAAAGTGAAATAAAAGCTTTGACTAGA(SEQ ID NO: 161) >NP_001315538.1 T-cell surface antigen CD2 isoform 1precursor [Homo sapiens]MSFPCKFVASFLLIFNVSSKGAVSKEITNALETWGALGQDINLDIPSFQMSDDIDDIKWEKTSDKKKIAQFRKEKETFKEKDTYKLFKNGTLKIKHLKTDDQDIYKVSIYDTKGKNVLEKIFDLKIQERVSKPKISWTCINTTLTCEVMNGTDPELNLYQDGKHLKLSQRVITHKWTTSLSAKFKCTAGNKVSKESSVEPVSCPGGSILGQSNGLSAWTPPSHPTSLPFAEKGLDIYLIIGICGGGSLLMVFVALLVFYITKRKKQRSRRNDEELETRAHRVATEERGRKPHQIPASTPQNPATSQHPPPPPGHRSQAPSHRPPPPGHRVQHQPQKRPPAPSGTQVHQQKGPPLPRPRVQPKPPHGAAENSLSPSSN (SEQ ID NO: 162) Mouse CD2>NM_013486.2 Mus musculus CD2 antigen (Cd2), mRNAGCCTCACCACAGTCCTGACAGAAAGAACTCAGAGTCACCCCTGGGAAAAGAACTCTAAAGATGAAATGTAAATTCCTGGGTAGCTTCTTTCTGCTCTTCAGCCTTTCCGGCAAAGGGGCGGACTGCAGAGACAATGAGACCATCTGGGGTGTCTTGGGTCATGGCATCACCCTGAACATCCCCAACTTTCAAATGACTGATGATATTGATGAGGTGCGATGGGTAAGGAGGGGCACCCTGGTCGCAGAGTTTAAAAGGAAGAAGCCACCTTTTTTGATATCAGAAACGTATGAGGTCTTAGCAAACGGATCCCTGAAGATAAAGAAGCCGATGATGAGAAACGACAGTGGCACCTATAATGTAATGGTGTATGGCACAAATGGGATGACTAGGCTGGAGAAGGACCTGGACGTGAGGATTCTGGAGAGGGTCTCAAAGCCCATGATCCACTGGGAATGCCCCAACACAACCCTGACCTGTGCGGTCTTGCAAGGGACAGATTTTGAACTGAAGCTGTATCAAGGGGAAACACTACTCAATAGTCTCCCCCAGAAGAACATGAGTTACCAGTGGACCAACCTGAACGCACCATTCAAGTGTGAGGCGATAAACCCGGTCAGCAAGGAGTCTAAGATGGAAGTTGTTAACTGTCCAGAGAAAGGTCTGTCCTTCTATGTCACAGTGGGGGTCGGTGCAGGAGGACTCCTCTTGGTGCTCTTGGTGGCGCTTTTTATTTTCTGTATCTGCAAGAGGAGAAAACGGAACAGGAGGAGAAAAGATGAAGAGCTGGAAATAAAAGCTTCCAGAACAAGCACTGTGGAAAGGGGCCCCAAGCCGCACTCAACCCCAGCCGCAGCAGCGCAGAATTCAGTGGCGCTCCAAGCTCCTCCTCCACCTGGCCATCACCTCCAGACACCTGGCCATCGTCCCTTGCCTCCAGGCCACCGTACCCGTGAGCACCAGCAGAAGAAGAGACCTCCTCCATCAGGCACACAGATTCACCAGCAGAAAGGCCCTCCTTTACCCAGACCCCGAGTTCAGCCAAAACCTCCCTGTGGGAGTGGAGATGGTGTTTCACTGCCGCCCCCTAATTAAGAAGGCAGAGTTCGTCATTTCCAATAAAAAGCTGTGTGGATTTATCTTC (SEQ ID NO: 163) >NP_038514.1 T-cell surface antigen CD2 precursor[Mus musculus] MKCKFLGSFFLLFSLSGKGADCRDNETIWGVLGHGITLNIPNFQMTDDIDEVRWVRRGTLVAEFKRKKPPFLISETYEVLANGSLKIKKPMMRNDSGTYNVMVYGTNGMTRLEKDLDVRILERVSKPMIHWECPNTTLTCAVLQGTDFELKLYQGETLLNSLPQKNMSYQWTNLNAPFKCEAINPVSKESKMEVVNCPEKGLSFYVTVGVGAGGLLLVLLVALFIFCICKRRKRNRRRKDEELEIKASRTSTVERGPKPHSTPAAAAQNSVALQAPPPPGHHLQTPGHRPLPPGHRTREHQQKKRPPPSGTQIHQQKGPPLPRPRVQPKPPCGSGDGVSLPPPN (SEQ ID NO: 164) Human LFA-3>NM_001779.3 Homo sapiens CD58 molecule (CD58), (CD58)transcript variant 1, mRNAGAACTTAGGGCTGCTTGTGGCTGGGCACTCGCGCAGAGGCCGGCCCGACGAGCCATGGTTGCTGGGAGCGACGCGGGGCGGGCCCTGGGGGTCCTCAGCGTGGTCTGCCTGCTGCACTGCTTTGGTTTCATCAGCTGTTTTTCCCAACAAATATATGGTGTTGTGTATGGGAATGTAACTTTCCATGTACCAAGCAATGTGCCTTTAAAAGAGGTCCTATGGAAAAAACAAAAGGATAAAGTTGCAGAACTGGAAAATTCTGAATTCAGAGCTTTCTCATCTTTTAAAAATAGGGTTTATTTAGACACTGTGTCAGGTAGCCTCACTATCTACAACTTAACATCATCAGATGAAGATGAGTATGAAATGGAATCGCCAAATATTACTGATACCATGAAGTTCTTTCTTTATGTGCTTGAGTCTCTTCCATCTCCCACACTAACTTGTGCATTGACTAATGGAAGCATTGAAGTCCAATGCATGATACCAGAGCATTACAACAGCCATCGAGGACTTATAATGTACTCATGGGATTGTCCTATGGAGCAATGTAAACGTAACTCAACCAGTATATATTTTAAGATGGAAAATGATCTTCCACAAAAAATACAGTGTACTCTTAGCAATCCATTATTTAATACAACATCATCAATCATTTTGACAACCTGTATCCCAAGCAGCGGTCATTCAAGACACAGATATGCACTTATACCCATACCATTAGCAGTAATTACAACATGTATTGTGCTGTATATGAATGGTATTCTGAAATGTGACAGAAAACCAGACAGAACCAACTCCAATTGATTGGTAACAGAAGATGAAGACAACAGCATAACTAAATTATTTTAAAAACTAAAAAGCCATCTGATTTCTCATTTGAGTATTACAATTTTTGAACAACTGTTGGAAATGTAACTTGAAGCAGCTGCTTTAAGAAGAAATACCCACTAACAAAGAACAAGCATTAGTTTTGGCTGTCATCAACTTATTATATGACTAGGTGCTTGCTTTTTTTGTCAGTAAATTGTTTTTACTGATGATGTAGATACTTTTGTAAATAAATGTAAATATGTACACAAGTGA (SEQ ID NO: 165) >NP_001770.1 lymphocyte function-associated antigen 3isoform 1 [Homo sapiens]MVAGSDAGRALGVLSVVCLLHCFGFISCFSQQIYGVVYGNVTFHVPSNVPLKEVLWKKQKDKVAELENSEFRAFSSFKNRVYLDTVSGSLTIYNLTSSDEDEYEMESPNITDTMKFFLYVLESLPSPTLTCALTNGSIEVQCMIPEHYNSHRGLIMYSWDCPMEQCKRNSTSIYFKMENDLPQKIQCTLSNPLFNTTSSIILTTCIPSSGHSRHRYALIPIPLAVITTCIVLYMNGILKCDRKPDRTNSN (SEQ ID NO: 166) Human CD48>NM_001778.4 Homo sapiens CD48 molecule (CD48),transcript variant 1, mRNACTTTTTCTAGCCAGGCTCTCAACTGTCTCCTGCGTTGCTGGGAAGTTCTGGAAGGAAGCATGTGCTCCAGAGGTTGGGATTCGTGTCTGGCTCTGGAATTGCTACTGCTGCCTCTGTCACTCCTGGTGACCAGCATTCAAGGTCACTTGGTACATATGACCGTGGTCTCCGGCAGCAACGTGACTCTGAACATCTCTGAGAGCCTGCCTGAGAACTACAAACAACTAACCTGGTTTTATACTTTCGACCAGAAGATTGTAGAATGGGATTCCAGAAAATCTAAGTACTTTGAATCCAAATTTAAAGGCAGGGTCAGACTTGATCCTCAGAGTGGCGCACTGTACATCTCTAAGGTCCAGAAAGAGGACAACAGCACCTACATCATGAGGGTGTTGAAAAAGACTGGGAATGAGCAAGAATGGAAGATCAAGCTGCAAGTGCTTGACCCTGTACCCAAGCCTGTCATCAAAATTGAGAAGATAGAAGACATGGATGACAACTGTTATCTGAAACTGTCATGTGTGATACCTGGCGAGTCTGTAAACTACACCTGGTATGGGGACAAAAGGCCCTTCCCAAAGGAGCTCCAGAACAGTGTGCTTGAAACCACCCTTATGCCACATAATTACTCCAGGTGTTATACTTGCCAAGTCAGCAATTCTGTGAGCAGCAAGAATGGCACGGTCTGCCTCAGTCCACCCTGTACCCTGGCCCGGTCCTTTGGAGTAGAATGGATTGCAAGTTGGCTAGTGGTCACGGTGCCCACCATTCTTGGCCTGTTACTTACCTGAGATGAGCTCTTTTAACTCAAGCGAAACTTCAAGGCCAGAAGATCTTGCCTGTTGGTGATCATGCTCCTCACCAGGACAGAGACTGTATAGGCTGACCAGAAGCATGCTGCTGAATTATCAACGAGGATTTTCAAGTTAACTTTTAAATACTGGTTATTATTTAATTTTATATCCCTTTGTTGTTTTCTAGTACACAGAGATATAGAGATACACATGCTTTTTTCCCACCCAAAATTGTGACAACATTATGTGAATGTTTTATTATTTTTTAAAATAAACATTTGATATAATTGTCAATTAACTGAA (SEQ ID NO: 167)>NP_001769.2 CD48 antigen isoform 1 precursor [Homo sapiens]MCSRGWDSCLALELLLLPLSLLVTSIQGHLVHMTVVSGSNVTLNISESLPENYKQLTWFYTFDQKIVEWDSRKSKYFESKFKGRVRLDPQSGALYISKVQKEDNSTYIMRVLKKTGNEQEWKIKLQVLDPVPKPVIKIEKIEDMDDNCYLKLSCVIPGESVNYTWYGDKRPFPKELQNSVLETTLMPHNYSRCYTCQVSNSVSSKNGTVCLSPPCTLARSFGVEWIASWLVVTVPTILGLLLT (SEQ ID NO: 168) Mouse CD48>NM_007649.5 Mus musculus CD48 antigen (Cd48),transcript variant 1, mRNAATACGACTTCCGGTTTTGGGTTTTGCTTCCTGATTGAAGGGCAGGCGCCCTGACTTCTCTTACAGTTGTCTCCAGTGTTCTGGGGAAGCTTCTCTAAGTATTATGTGCTTCATAAAACAGGGATGGTGTCTGGTCCTGGAACTGCTACTGCTGCCCTTGGGAACTGGATTTCAAGGTCATTCAATACCAGATATAAATGCCACCACCGGCAGCAATGTAACCCTGAAAATCCATAAGGACCCACTTGGACCATATAAACGTATCACCTGGCTTCATACTAAAAATCAGAAGATTTTAGAGTACAACTATAATAGTACAAAGACAATCTTCGAGTCTGAATTTAAAGGCAGGGTTTATCTTGAAGAAAACAATGGTGCACTTCATATCTCTAATGTCCGGAAAGAGGACAAAGGTACCTACTACATGAGAGTGCTGCGTGAAACTGAGAACGAGTTGAAGATAACCCTGGAAGTATTTGATCCTGTGCCCAAGCCTTCCATAGAAATCAATAAGACTGAAGCGTCGACTGATTCCTGTCACCTGAGGCTATCGTGTGAGGTAAAGGACCAGCATGTTGACTATACTTGGTATGAGAGCTCGGGACCTTTCCCCAAAAAGAGTCCAGGATATGTGCTCGATCTCATCGTCACACCACAGAACAAGTCTACATTTTACACCTGCCAAGTCAGCAATCCTGTAAGCAGCAAGAACGACACAGTGTACTTCACTCTACCTTGTGATCTAGCCAGATCTTCTGGAGTATGTTGGACTGCAACTTGGCTAGTGGTCACAACACTCATCATTCACAGGATCCTGTTAACCTGACAAGAACTCTTCTCACCCAAGAAGGCAACTTGGAAGCACAGAGTCTTGCCTTCATCCCTAGCAGTGTTCCTAGCCAGCGAAGCAACTCTGGCTCTATTGGACAAAGGAAAATGTGTTACTGAACGTCTGCGAGAGTTTGCATGCATGCTCTATGAAACAAGCACAGGACCTTGTACAGTGCTCCACCACTGACCTGTGTGCCCAGTCCTTTACAAAGATTTCAAATCAACCTTTTAAAAACTGTGCATAATATCTAATTTTATATACCCTAGTTGTTTCCCAACATATATTAAAGATAAATGCATTCTTTTTACCAAAATGTGACTATATTATTTTCATGTTTTCATATCTCTTTTTAAAATAAATTCTTTTAAAAAACT (SEQ ID NO: 169)>NP_031675.1 0048 antigen isoform 1 precursor [Mus musculus]MCFIKQGWCLVLELLLLPLGTGFQGHSIPDINATTGSNVTLKIHKDPLGPYKRITWLHTKNQKILEYNYNSTKTIFESEFKGRVYLEENNGALHISNVRKEDKGTYYMRVLRETENELKITLEVFDPVPKPSIEINKTEASTDSCHLRLSCEVKDQHVDYTWYESSGPFPKKSPGYVLDLIVTPQNKSTFYTCQVSNPVSSKNDTVYFTLPCDLARSSGVCWTATWLVVTTLIIHRILLT (SEQ ID NO: 170) Human CD226>NM_006566.4 Homo sapiens CD226 molecule (CD226),transcript variant 1, mRNAGCAGATGGGAAGAAGCGTTAGAGCGAGCAGCACTCACATCTCAAGAACCAGCCTTTCAAACAGTTTCCAGAGATGGATTATCCTACTTTACTTTTGGCTCTTCTTCATGTATACAGAGCTCTATGTGAAGAGGTGCTTTGGCATACATCAGTTCCCTTTGCCGAGAACATGTCTCTAGAATGTGTGTATCCATCAATGGGCATCTTAACACAGGTGGAGTGGTTCAAGATCGGGACCCAGCAGGATTCCATAGCCATTTTCAGCCCTACTCATGGCATGGTCATAAGGAAGCCCTATGCTGAGAGGGTTTACTTTTTGAATTCAACGATGGCTTCCAATAACATGACTCTTTTCTTTCGGAATGCCTCTGAAGATGATGTTGGCTACTATTCCTGCTCTCTTTACACTTACCCACAGGGAACTTGGCAGAAGGTGATACAGGTGGTTCAGTCAGATAGTTTTGAGGCAGCTGTGCCATCAAATAGCCACATTGTTTCGGAACCTGGAAAGAATGTCACACTCACTTGTCAGCCTCAGATGACGTGGCCTGTGCAGGCAGTGAGGTGGGAAAAGATCCAGCCCCGTCAGATCGACCTCTTAACTTACTGCAACTTGGTCCATGGCAGAAATTTCACCTCCAAGTTCCCAAGACAAATAGTGAGCAACTGCAGCCACGGAAGGTGGAGCGTCATCGTCATCCCCGATGTCACAGTCTCAGACTCGGGGCTTTACCGCTGCTACTTGCAGGCCAGCGCAGGAGAAAACGAAACCTTCGTGATGAGATTGACTGTAGCCGAGGGTAAAACCGATAACCAATATACCCTCTTTGTGGCTGGAGGGACAGTTTTATTGTTGTTGTTTGTTATCTCAATTACCACCATCATTGTCATTTTCCTTAACAGAAGGAGAAGGAGAGAGAGAAGAGATCTATTTACAGAGTCCTGGGATACACAGAAGGCACCCAATAACTATAGAAGTCCCATCTCTACCAGTCAACCTACCAATCAATCCATGGATGATACAAGAGAGGATATTTATGTCAACTATCCAACCTTCTCTCGCAGACCAAAGACTAGAGTTTAAGCTTATTCTTGACATGAGTGCATTAGTAATGACTCTTATGTACTCATGCATGGATCTTTATGCAATTTTTTTCCACTACCCAAGGTCTACCTTAGATACTAGTTGTCTGAATTGAGTTACTTTGATAGGAAAAATACTTCATTACCTAAAATCATTTTTCATAGAACTGTTTCAGAAAACCTGACTCTAACTGGTTTATATACAAAAGAAAACTTACTGTATCATATAACAGAATGATCCAGGGGAGATTAAGCTTTGGGCAAGGGCTATTTACCAGGGCTTAAATGTTGTGTCTAGAATTAAGTATGGGCATAAACTGGCTTCTGAATCCCTTTCCAGAGTGTTGGATCCATTTCCCTGGTCTTGGCCTCACTCTCATGCAGGCTTTCCTCTTGTGTTGGCAAGATGGCTGCCAACTCTTGGCAATTCATACATCCTTGTTTCTGTCTGGTAGAGAGTTTGCTTCTCAAATGGAGCAAACAAATTTGATTATTTTTTCATTGTTAAATAGGCAACATGACCAGAAAGGATGGAATGGCTTAAGTAAACTAAGGGTTCACTTCTAGAGCTGAGAAGCAGGGTCAAAGCACAATACTGGGCAATTCAGAGCATGGTTAGAAGAGGAAAGGGGAGTCTCAAAGCTGGAGAGTTTACCAACAAATATTGACTGCAGTGATTAACCAAGACATTTTTGTTAACTAAAAAGTGAAATATGGGATGGATTCTAGAAATGGGGTATCTCTGTCCATACTTCTAGAATCCACTCTATCAGCATAGTCCAGAAGAATACCTGGCAGTAGAAGAAATGAATATTCAAGAGGAAGATAAATGCGAGAGGGCAATCCTTTACTATTCTCATATTTATTTATCTCTCATTCTGTATAGAATTCTTGCCGCCATCCCAGGTCTAGCCTTAGGAGCAAATGTAGTAGATAGTCGAATAATAAATAACTTAATGTTTTGGACATATTTTGTCTACTTTTGAGAATTATTTTTAATATGTAAATTCTCTCAAAAGGGTCAGGCACCTAGTTATTATTTTTTAATGATTATGTGAAAGTTGAATATAATATACCACTAAAAGTGACAGTTGAAAGTGGTGGCATAGGACGGTAGGGTAGAAATTTGGGAGGGAAAAAAGAAATTGGGAGGGTACAGGCAACAGGAGAAAGGAATCAAACCACAGAAAAATACAAAGGGAAACTTCTGCTTCACTATTCAGACAAAGACAGCCCTAATGACATCACCAACAGTCAAAGCAATTAGAGACCATACCTAATATTGTTTAAATTCTAGATGTAGGCTAACAATGAAAAGTATTTGCCAAACTGAATAAAACTGTCATGGTTACCTTGAAAGGACAATGGTTATTGTTAAATATAGTGATCATTCATGTCTAAAAGATTCATTATTTATCTCTAAAGATTTCTAAAGACCACCATCTAGAAAAGATTCATTATGAAGGCTGTATTTAAATATCAAAGTTGTGGACTTCATGATAATCTTAAATAAAGCAAATCCAAATTCTCCTGTTGCCTAGACAGATTCTAAGATGTAATTTACACTTTTAAGCTAATTAGTGAGTATTTTATGATTTTAGCCTTAAACACCATGTATGCCAAATAATGCACTTGTTTTGTGAATTACAGAAATGGTAAGTGCCCACATTTCTGTGAATTATAAAATTTGTGAGTTTCTTTTAACCCTTTTCAGGAGTGAAAAAATAAAAACGACCATTTCCTGGTTGTGCTTAAGTATATGCAAGAAGGGTAAACTCTCATTTTTATTATGTTTGCTTAAAGATCTTTTTATACCTGGATTCATGAAATGTTTCCACAAATATATTAGTGTAACAAACTTGAAAGGCAGTTTACAAGAAAGCACTCTACTATCAGATCAATCAAAGATTCTGTGAGTGAATTTATTGGTTTGCATGGTGAAGCAAGCTTAGCATCAATTAAAAGGTAAATAATTTCTTTTCTGAATGGTAAAGACAATCAAAATATTACTTTCTGGAAAACTCCAATAACCAAATTCTCAATGATTAGTGTATGTGAGCAGGAAAACATTTTTACAGTTGTAGTATGGGGAAATATAAATCCAATTTTAAGAGAGAAAATTATGACTGGGTGTGGAAGGGACAGTATAGTCAGATACCATTGTCATGGTGGTTTTTACTGGGAACTTCATGAAAGACTTTTGTAGCAAACCACTGCAGTATTGCAAAGCCTCCAGAACATTTGGAACTTGTCTCTTTTTCCTTGTGTGTGTTTGTGTTTTTGGTCTCTCATTCAAAATATTGATGAGAACTATTTACTCTGTCCTTTCTTCTCTATATATTCTTCCTCTACAGAGTGTAGGGTTTTTTCAGGAATTTGGAGCCATCTGAAGTCCTCCCAAAAATTCTCTGACGTCTTCTGATGCTCCTGTTATACCCTCAGGGGTAATGCTTGTGAAATTCCATTCATTCATTTTCTTTCTCTGGACATCTTTACTTACCAAAGCACTTTCATTGTCATCTTTTTAACATCATTCTTAATTCGTGATAGTTTTGGGACTCTCCCTAGTGTATGTTTCTCCCCCTCTACTCTTTTGCACCTATGATTCTGATTGTTACTAAGAAAGCAGATGAAAAACAGATCCACAGAATAAACGATCAGAATTCCAGTAAATTCTATTTTAAATACAGATACTTTTTACAAGTTGCTGCTTTGGAAGCAAAATGCTTCTTAAGTTTTACATATATATATATATATATACATATATATATACACATATAATTTATATCGATGGATAATACATTAAGAATCTATGCTTCCTTTGAATGCCATTAATATTTATGTTAAAGTAACCAATGAAAGGAAATTACTTTGTTATAATAAGATAGGAAGACTTGTTAATGGAGTACACAGTTTTGTCAGGGAAAGAACACATCTTATTGAACTATGATGACTATGCATTGACTATATTATTATAAGAGATACCTTCAAACTTTATTTAAAGAACTTTAGGTATAATATGTTGAGAAAATAAAATAGAAATTTCATTTACTTGTAATCATGCTTAAAATGGGAGGCAGGTAGGTGAAGATATAATTTTTAGTAAAAACTCCAATTTATGTTTTAAGTAATTCAGTGTATTACTAAAATACTATATATATAAACTTAAAATACATGGGTTATCAATTTAAAAGACAAAGTAAGTAAAAATACTTTTAGTAGGCATTCGTGGATTGTGAACATCCAAGTTATATTGGTTTGTATAGAATGGCATTAAGTAAAAATTACAGCTGTATAACAGTAGTTTTCTAAATTGAGAGAGTCCACATTGTAATTAGAGATCACTGTGACCAAAATGCTTCTCCTTGATTTATAATGATGTACTGTATTTTGTACTGCTTATATGAAATTTCAGCAAGATTGACGATATTATAAAGATGCTTATAAAGTGTAAGTGGAGACGCTAAATTGTGAGTACAAAGTTTCTTTTTCACAACAGTGATAAGAAAATATCTTTAAAAAATATAAGACAATATAAACATGTCATCATTAGTTTAGCTACTATTAAAATGTAACATCTAGAAAGTACTGATCTCCACCTTCAGACTTCTGTATAAGTATATTTTTTCACTGATCTGTTCATTAGAGTTCTTCCAGCCAAGACTCTGGGCTCTTAAAACATGTATCTGAAAACTAAAAACAAGTTAATTTTTTTAAAAGCTTCTCTATTTCTAGTGATTCAATAGGTAGAAAAATAGCTTCTAGAATTAACTGCAATGCTTTCTAAGGAAATTTTATAAATCCTCAAGGTCGGTTTACACATATTTTTCCAGATTCAGAGCACTAACTATCTTGTAAGATGTAAGAAAAGGTCCATTTGGAAGTATGAGTAATAAATGTCTGGGATAATTCTGGTTTATTTCGTATTATCCTTGTTAGAATAAGTTATATGGTCAACCTGTTCAGAACACTTTTTCTAGTGTTAGTGTGTACTTTTGGATTTTTGGTTCTTGTAGGGTATAGAAATATTTTCCTTTGTCTTGTATTCTGTTGTTTTGAATGAATAAAACACAATGTTTCACGATCACTACTTTCATTTGCCATGGAGAAATAGCAGGGAAAAATTTCTACAGAATAAAATTAACTGATGAATTACATGCAGAAAAAATTCAAATCAATGATACATTGTAATTTTTATCTCAATGCAATGTTCTTTGTATTTTATTTTATTATTATTTTTTTGAGACGGAGTTTCACTTTTGTTGCCCGGGCTGGAGTGCAATGGCACAATCTCGGCTCACCACAACCTCTGCCTCCCGGATTCAAGTGATTCTCCTGCCTCAGCCTCCTGAATAGCTGGGATTACAGGCATATGCCAACATGCCTGGCTAATTTTGTATTTTTAGTGGAGACGGGGTTTCTCCACGTTGGTCAGACTTGTCTTGAACTCTGGACCTCAGGTGATCCACCTGCCTCAGCCTCCTAAATTGCTGGGATTACAGGCATGAGCGACCACTCCTGGCCTTGTTCTTTGTATTTTATAAGTGCATGTAGTGCAAAGGGTCAAAGGGCTTTACAGGTTTTTTGTTTGTTTGTTTTTGTTTTTCCCGAAACATAGTAGTCCCTTGCCCTTCCTCATTTTTGTTACCTTGAGACAACAAATTTTACTACTTCTAACTCATTATTTTATTTATGTTCACTTTTCTGAATAGCATGCTTATGACACTAATACTTTTTTTTTCAATTTTAGACATTCATTATTCATTTAGATGTCTTTCTCTCCCCAAACTCACCACATAAAATACTCTTCTCATGTCTCTTTCAGAAATATTTGTATTAAAATATGATTATATCAATATTTGGCATTTATTTCTTATGACCTTGCCAGTACTCTTAGTTAAACTACATGGTAAAAATGATTTTGCTTTCCCTCCTACATAACTTTTTTTCCACCTAGAGCTAATAATTGTCATTCTGGGGACTGACTTTTTCTGTATTTACCATAAATTGACCTGAAACTCCCCTGTGATGCAGCAGGAATTCTACCAACGTCAACTTCCTTAGAAAGACTCCATTAGAAGCTTGACTTGGGGCTAGAAGGAGAGGCACACAACTGCCATCCTGGTGTCTCCCTTCATCCAGAAAAAGGGGGAGGAATACATGAAACCTAGAATCCACTCTAAAACATTTTCCAGAACAAAAGGACATGTGTTTCCGTGTTGTAAATGTTTAACGAGTGCCCATAACAAGGAATAATAAGTCTATTATGTTTGCTTTTGTGTCTGTAAAAGTTGGGGGTATTGGTTGTAAGCACGAAAACAGATACTGACTGTTGAAGAAAAAAAAAAATACGAGGTCAGGAGTTTGAGACCAACTTGGCCAATATGGTGAAACCCTGTCTTAGTAAAAATAGAAAAATTAGCCAGGCCTGGTGGCACGCACCTGTAGTCCCAGCTACTTGGGAGGCTGAGGCAGAAGAATCGCTTGAACCCGGGAGGCAGAGGTTGCAGTGAGCCAAGATCGCACCACTGCACTCCACCCTGGGCAACAGAGCGAGACTCCGTCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGTTAAGTATTTGAACATAGGGGTGGCTCATAGAATTCCCAGGACACCCGATGGAGTAGGCTTGCAAAACACAACATGTGGCAACTCCAGTGGGAAACGAGGCAGGAAACACTCGTTTCCTGCAGAAAGCAACAATTTGGGCTTCGATACCCTCCCTAGAACACAGGGCAGTGAATCTGAGCAGCATCAGTACCCCACGTTCGGATGAGTCCTGAGCCCCTATTTTTATTCACTGACTTATTCCAAAATCAGTGTCTCTTAAATATATCTGGAAGGCAGCAGCTTGTATCTCCCCCTTCAGCTTCCATAGTGGCAGTCAGGGTACAACTTACTTTCCAAACAGAACACACTGCGACATTCCCTCCAGGCTCGTTGAAGAACTTCAACTGACAAATGTCCCTCCTCGACCAGATGATAGTTTTCTTAAAGGCAGGGTTTAATATACCCTTTTATAAATGTTTCAAGGCCCTGTGTAATACCTGAGTTTATTCCAGATGTAACTAAATATATCCAAGATTGTTTTAAAATAAATTGCTGAAAAAACAAATAAATACAGTTAGTATCTATATCAATATTCTCAGTTGGCAGTTTTGCAATAATGGCCGATAGTTCATTTTTAGTAACACTATTGACATTGCATTTGGATATTAGGGTTTACTAATCATCCGCATGTATACATTGCATATTTTTCTAGACTTTAACTTTATTCAAATCTATTGATTTTTAAACCTGCAACTTATGTCTAGACACAGGTATACCTTTACAAGAACTACCATTTTTTTTGGTAACATACTACCTCCAAAATTTCAAGTAAGAAGTTGATTTTTGTCCATTTTTAAATGGAAAACTTGTAATCAAAATGCCACAAAATTATACTGTGTATCATTTGACCTATAGAAACCAATATTATTACAGGAAGAAAGCAGAGCCAATCTTCTACCTGTGGTCAAATAAGTGGAGGCCCTTTCTAGACTAAGTTCTCATGAGTTTAAAATACCAAGCATAAGTTCTCCAAATTCCTGAAAAGGAAGCCTTGTGTTGTATTGCCCAGCCATATTTGTAAGACATAAAAATAAAACTTGAGAAGAAGCTATGATAACTTACTTTCTTCATTCTTCAAAATTTACATAATCTCAACTGATTTTATGTTTTTATGAAAATGCATTCTTAAGATATATCCTTATTCAATCATGTATTCATTACATCCTTTATGCCAGGTATCCAAAAGTACTTACAGTGACTAAGACCATTATTCTTTGATCAGCTGCCTGAGTAAGACTTTGAGCTCTCCAATATACTCTCAGTGATACTAAGTTTTCTGAGTAACAGCTTTGGATGTGGCTTCAGTTGAGCTGATTTATCCCACACTTTATTTTTATCGTATAATGGTCCTCAGAAGCAAATTTTGATTTTAGCTCACATAAAAAATGTACAAAGAAATGTAATGGCTCAGTAGCTTCTAGAGATAGAGATTACTCTTCTAACCTTTCTGTAATTTTGTATGTCTATTTTATAATTCTTTCAATGTCTAATGAATAGCTATCTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCAGGCTGGAGTGCAGTGGTGCGACCTCGGCTCACCGCAAGCTGCGTCTTCCAGGTTCACGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTTCAGGCGCCCACCACCATGCCCAGCTAATTTTTTTGTATTTTTAGTAGAGACGGGGTTTCACCGTGTTAGCCAGGGTGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAACGTGCTGGGATTACAGGAGTGAGCCACCGCGCCCGGCCTCCTTAGTTTCTTAAGGTGGAAGCCTAGATTATTGATTTTATATGTTGTTTTCTTTTCCAATAGTGGCACTTAATGCTATAAATTTCACTTTGTTCCACAAGTTTTGGTAAGCTCTATTTTTATTTTCATTTAGTCCAAAATATTTTAAAATTTCTTTTGATATTTCTTCTTTGAGCCATGAATTATTTACAATGTGTTGTTTAATCTCTATATATTTTGGGATTTTTCTACTTTATATCTCTTACAGATTTCTAACTTAATTTCATCATGTTTTAAAAACATTCTTTGTATAATTTCTATTCTTTTAAATTTTTCAGGTGTATTTTATGGCCCAGAATATGGTCTATCTTGTAGAATGTTTCATGTGATCTTAAGAAGAATGTTCATTCTGCTGTTGAGTGTAATATTCTACAAATGTCCATTAGATTAAACTGATTGATACCACCGTTCAGATTATCTATATCCTTTCTGATTTTCCCTCTTCTTGATCTATCACATACTGACAGATCAAGTGATCAAGTCTCGTTAAAGACTGCAAGTAAAATAGTGGATTTTTCTATTTCTCCTTGCAGTTTTGTTAGTTTTTGTCTCATGTATCTTGATACTCTTGTTAGTACATATACTTTCAGAATCGTTAGGTTTTCTTGGAGAATTGACCCCTTTACCACATGTAATGTCCCTTTTATTCTTGATAATCTTTCTTGTTCTGTCTGCTTTTTCTGATATTAACATAACTTTCAGTTTTTTAAAAAATTAACATTAGCATCTCACATCTTTATCCTTTTAATTTTAAATTATCTAAATATTTATATTTAATGTGCCTTTCTTATAGACAATGTATAGTTGCGTCTATTTGTAATTTCCCCACTTTTCTTACTTAAAAATGTTGTAGATATATAGGAGTTGTATATATTTGGGGGGTACATGTGATGTTTTGATACCTGTATACAATATGTAATGATCATATTGGGTAATCGTGATATCTGTCACCTCTAACATTCATCTTTTTTGTGTGTTTAAACCCACCACTTCTAATTGGTACATTTAGATTATTCAAATTTAAGTGATTATTGATATAGTTGGATTAATATCTACTATGTTTGTAACTTTTCTATCCTTGCACTCGTTCTTTCTTTTTTATCCTCCTTTTTCTGTGTTCTCTGATTTTAACTGGGGTTTTTACATGATTTAATTTTCTCTCGTGGCATATCTTTCATTGATCAACCTAGGTTTTTCTCCTTTTCCCCTCTTTTTTTTGGTATTTATTCTATTTAGTGTTATCTGAGCTACCTGAGTTGGTGTCTATCACTAATTTTGGCAAGTTCCCAGACGTTATTACTTCTAACATTCTTTTGCTCCATTCTTTCTTCTTCTTCAATTATTCCATAGTCTTGAATATTCTGGGTTTTTCCCACTCTTTGAATTTTAGTTTGAAAAGTTTCTATTGGCCTAGCTTCAAAGTCATTCATTCTTCCTTCGGGGTTCCAAGTCAACTGATAATTGCATCAAAGATATCCTTCCTTTCTATTACTATGTTTTTTATTGCTACCATTTCTTTTTTATTCCTTCTTAGTGTTTCCATCTTTCTTCTTACATTATCCATCTGTTGTCTATTTTTTTCATGAGAGCTCTTAACATATTAATGATAAGTTCCATGTCTGATAATTCTGACACGTGTCATGTCTCTATCTGGTTCCAATGATTGCTTTATCTCTTCAGACCATGACTTTTCTTGCCTTTTGACGTTCTTTGACATTTTTTTTGAATTTTTTGTTGCAAGCCAGATCTGGTGTGTTATGTAATAGGAACAGGTAAATAAGTCTTTAGCTTGCAGACTTATCTTAATCTGACTAACTATTAGACTGTGTTTAAAGTCTGTTATAACCATAGGTGCTAAATTTCTTCAAATTCCTCTAGTGTCTTTGTTTTGTTTGTTCATGTGTTTTTCCCCTTCTTGAGTTCAGGCTTCCCTAAGTGCTCCTCTTCAGAGAGACTTTCTGTCTTTCAGCTCTTTCCTCTGCAATTCACTGTTACTATACTGGAGCCCTGTTGGTGTAGTACTAAGCTGTGGGAAAGGAGAGTGCTCTGTAATCTTACAGTGAAATCTCAGTOTTTTAGTGGGTCTGTGTCTGGGACATTCACAGAGCTTCTCCAGTGGTATTGCTTCCTCATCCTCAACTCTCTTTCCTGGCTGCAGCATTCCCAATGTATTTCTTTGAAGGCCTGCCCCCTGTTGACTGTTATTTTCCCTCTTTCCTTAAGTGGGACAGGGAGACTTCAGGGGCTGGGATGAGGTTTGGGAATTGTGCTTGGCAGAGTCCTTTCCATCTTTGTTACCAAGAAGGTTCATGGCTTATTTCTCAATGGATGTCCCTCTCTATCTGTTGCCAGAGCCACGAGGAAATTTTTCTTGGATCCTCATAATGAGAACCTTGGAGTTTCCTACTGGAAAAGCCCTTGAATGTGTGGAGTGCCTCAAGAGCACAGCCCCCATGGGTTTCTTGCTCACACCAGTCCACAAACAGATGCCAGCAATTCACCCAACTTACCATATAAAGGCTCATACTAGTTTATGGCTCCAGTGCTTTGACTCCAGATAAATGGCTATTGGTTGCGTATCTCTCTGGATGTATCTGTATCTCCAGATTTTGGGGTGGCAGTTTGCTCAGGACCTTGGTTCTCTAATAGGTCTAATAAGAAAAGTCATTGATTTTCAGCTTTCCAACTTTCCAGCTTTGTCTTGTTATAAGCATGGCAGCAACATCTTCCATGCCTTAACATGATGACACTAAAGGCAGAAGTCGATCTCCATGTATAAACATTTTAACACATATGTTTTTTGTTATCGTGGTTTCTGACCTGTCTCTTTGCCCTGACTTTCTGATACTGCACTAGGGTTCCTGTTGCTGGACTCCATTCCATATGACTTGCTCTCGTCTAGGCTGCTCTTTGGCTCATCTTTATAAATCATGATCCAAAATGAAGCACATATTTATTTTTTAAATAAATATGAAATGAAGTATAGACATCAAACTGAAGATGAGTAGATCATACTGAGTTTCACTGTCTGTGCTTGGATCAACATCAGGCCTTATACAAATATTCAAGTCCAGAGGCAAAAGGTAATAAGGAAAATTTGTAGCACAAGCCACAAGGAGATAACATGTCAAGTCTATGCGATTGGAAATAAACTAAAGATGAACTGCTGGGGATGCTCACTCATCACAGAGCTCAGTCTAAAGCACCAGATTTCACAAGCATTTTTTGGGGGAAATTCTGTTAAAATGAAATATGAGTCACATGGTGGTGTTTCACTCATCATATGTGTTCAATATTAATTCATTTTAAGGTTTAGTTGCACAAAAGGTAAATGAGAATTAGAAGACTCCATGGGTAAGAGGAGCCACAGAAGTAAAGCATTGTCAAGGGTTCTATGTCTATATATTTAGATATTAGGCTTCTGAGAAAAAAACACAATAGGAAGGAAGATGAACACAACAGAGGGCAGAAGGTCTATACGTCCTGAGGCCTTTTATGCAACGTTTGTTTGTGGAATGTTTTTTAAGAATGTGTGAGAGTCATTTTAATGTGAAATAAAGACCTACGTCTACA (SEQ ID NO: 171)>NP_006557.2 CO226 antigen isoform a precursor [Homo sapiens]MDYPTLLLALLHVYRALCEEVLWHTSVPFAENMSLECVYPSMGILTQVEWFKIGTQQDSIAIFSPTHGMVIRKPYAERVYFLNSTMASNNMTLFFRNASEDDVGYYSCSLYTYPQGTWQKVIQVVQSDSFEAAVPSNSHIVSEPGKNVTLTCQPQMTWPVQAVRWEKIQPRQIDLLTYCNLVHGRNFTSKFPRQIVSNCSHGRWSVIVIPDVTVSDSGLYRCYLQASAGENETFVMRLTVAEGKTDNQYTLFVAGGTVLLLLFVISITTIIVIFLNRRRRRERRDLFTESWDTQKAPNNYRSPISTSQPTNQSMDDTREDIYVNYPTFSRRPKTRV (SEQ ID NO: 172) Mouse CD226>NM_178687.2 Mus musculus CD226 antigen (Cd226),transcript variant 1, mRNAACACAGAAGACTTCTTGACTTCAGGAGACACTGCTGTATGAAACAGTGCTTGCTATCAGTGGCTGCTGGAAGAGGCTGTGGTGGAAAGAAAACCTCAACTGCAGGCCAGAGTTGGTTCCCCAAAAGAGGCAAACTCCCAGTGCTAGCCAGAGGCTAGGAAGCTCTAAGCAACCCACTTATCTGCAAGGAGAGTTACGCCCAAAGAGCATCAAGTCCAACCTCCTGAACTGTTTCCAGAGATGGCTTATGTTACTTGGCTTTTGGCTATTCTTCATGTGCACAAAGCACTGTGTGAAGAGACATTGTGGGACACAACAGTTCGGCTTTCTGAGACTATGACTCTGGAATGTGTATATCCATTGACGCATAACTTAACCCAGGTGGAGTGGACCAAGAACACTGGCACAAAGACAGTGAGCATAGCAGTTTACAACCCTAACCATAATATGCATATAGAATCTAACTACCTCCATAGAGTACACTTCCTAAACTCAACAGTGGGGTTCCGCAACATGAGCCTTTCCTTTTACAATGCCTCAGAAGCAGACATTGGCATCTACTCCTGCTTGTTTCATGCTTTCCCAAATGGACCTTGGGAAAAGAAGATAAAAGTAGTCTGGTCAGATAGTTTTGAGATAGCAGCACCCTCGGATAGCTACCTGTCTGCAGAACCTGGACAAGATGTCACACTCACTTGCCAGCTTCCAAGGACTTGGCCAGTGCAACAAGTCATATGGGAAAAAGTCCAGCCCCATCAGGTAGACATCTTAGCTTCCTGTAACCTATCTCAAGAGACAAGATACACTTCAAAGTACCTAAGACAAACAAGGAGCAACTGTAGCCAGGGGAGCATGAAGAGCATCCTCATCATTCCAAATGCCATGGCCGCTGACTCAGGACTTTACAGATGTCGCTCAGAGGCCATTACAGGAAAAAACAAGTCCTTTGTCATAAGGCTGATCATAACTGATGGTGGAACCAATAAACATTTTATCCTTCCCATCGTTGGAGGGTTAGTTTCACTGTTACTTGTCATCCTAATTATCATCATTTTCATTTTATATAACAGGAAGAGACGGAGACAGGTGAGAATTCCACTTAAAGAGCCCAGGGATAAACAGAGTAAGGTAGCCACCAACTGCAGAAGTCCTACTTCTCCCATCCAGTCTACAGATGATGAAAAAGAGGACATTTATGTAAACTATCCAACTTTCTCTCGAAGACCAAAACCAAGACTCTAAGCTGCTCTTTTGGCCTGAACACATTAGTGATGACTTCTATGGCATGGAATTTTACCCATGATTTCCTTACCACTAGGATCTACATTGATAAAAAAAATTGATTAAATTTATTTCATCTCATATATAGAAGTACTTTATTACCTGGAAACATTCTTAATAGAGATTCATTAGAAAACCCAAATCTAATGTTCATGTGTTCAAGGAACCTTCTTCCATTATGTAACAGAACAGTCTAGAGAAGATTAAGGACCACATGGCTTTCTTGCTCTACTTGAAATTAATTGTGAGCATAAGCTTGTTTCTGGAGTCTTCTTACATTGTTGGTTCTACTTACATACTACTGGTCCAACTCTCATGCTGTTTCTCTCAGATGTTCCCATGATGGTTGCCAAGGACACTTGATAGAAAGACTACTGGTTAAACACAATAAACAAAGTTCATTATTCACTTATTAGCAAGAAGGTAGCATTATCATAAAGGATTAGATGACTTAAGTTAGCTATAGGTTCAAGACCTGGACTAAAGTATTACTTGGAAATTCTGAGTATTGCTAAAAAGGAGGATGAAAGGGACCTAGAAGTTGAGTTATTACTAAAAACTTTGAGTGCGAAGATATTACTCATTAACCAGATAACAAGTGAATATGCTGTAGCATCAACATAATTCAAAAGAGTAAAGAAATGGCTAGGAATGAGGTAGTTGTGTAATTATTTCTTCTCTTACTAGTTTCAAATAAATTCATCTCTAATTCTATAGAGAATTCTTGCCTCCCATTCAGGACTGGCCTTCTATACAGTGAGATGGTCCAGTAAGAAATAATTTTTATTAGTGTTTTTTCTATTTTGAGAATTATTTTAATATATATTTTAATATATAAACTTGTGAGTTAAATTTTTTTTTTGCAAAATTAGCACATGAAAAGAGATTGATGGTTTTAAGTAGTAGAACACAGTAGTGTAGGAATCTGAGAGCAGAGAGTTTGGGAGGGGGTGAAGAGAAAACAACATCACCAAATAGTGATATATAAGAGAAAATCTGTGCTTCAGAGTTTGATCAGGGCCATCTCTCCCAACTCTGCTGGAACTGAGAGAATGCACCTGATGTTGTCTCCATTTTAGATAGAGAAAAAAAAAACCCGAATATTTATAAAACTAAATAAAACTATAGTTACCTCAAAACTATGGGGATCACTATAACATAGAATAGAATAGAATAGAATAGAATAGAATAGAATAGAATAGAATAG (SEQ ID NO: 173)>NP_848802.2 CD226 antigen isoform a precursor [Mus musculus]MAYVTWLLAILHVHKALCEETLWDTTVRLSETMTLECVYPLTHNLTQVEWTKNTGTKTVSIAVYNPNHNMHIESNYLHRVHFLNSTVGFRNMSLSFYNASEADIGIYSCLFHAFPNGPWEKKIKVVWSDSFEIAAPSDSYLSAEPGQDVTLTCQLPRTWPVQQVIWEKVQPHQVDILASCNLSQETRYTSKYLRQTRSNCSQGSMKSILIIPNAMAADSGLYRCRSEAITGKNKSFVIRLIITDGGTNKHFILPIVGGLVSLLLVILIIIIFILYNRKRRRQVRIPLKEPRDKQSKVATNCRSPTSPIQSTDDEKEDIYVNYPTFSRRPKPRL (SEQ ID NO: 174) Human DR3>NM_003790.3 Homo sapiens TNF receptor superfamilymember 25 (TNFRSF25), transcript variant 2, mRNAGAAGGCGGAACCACGACGGGCAGAGAGCACGGAGCCGGGAAGCCCCTGGGCGCCCGTCGGAGGGCTATGGAGCAGCGGCCGCGGGGCTGCGCGGCGGTGGCGGCGGCGCTCCTCCTGGTGCTGCTGGGGGCCCGGGCCCAGGGCGGCACTCGTAGCCCCAGGTGTGACTGTGCCGGTGACTTCCACAAGAAGATTGGTCTGTTTTGTTGCAGAGGCTGCCCAGCGGGGCACTACCTGAAGGCCCCTTGCACGGAGCCCTGCGGCAACTCCACCTGCCTTGTGTGTCCCCAAGACACCTTCTTGGCCTGGGAGAACCACCATAATTCTGAATGTGCCCGCTGCCAGGCCTGTGATGAGCAGGCCTCCCAGGTGGCGCTGGAGAACTGTTCAGCAGTGGCCGACACCCGCTGTGGCTGTAAGCCAGGCTGGTTTGTGGAGTGCCAGGTCAGCCAATGTGTCAGCAGTTCACCCTTCTACTGCCAACCATGCCTAGACTGCGGGGCCCTGCACCGCCACACACGGCTACTCTGTTCCCGCAGAGATACTGACTGTGGGACCTGCCTGCCTGGCTTCTATGAACATGGCGATGGCTGCGTGTCCTGCCCCACGAGCACCCTGGGGAGCTGTCCAGAGCGCTGTGCCGCTGTCTGTGGCTGGAGGCAGATGTTCTGGGTCCAGGTGCTCCTGGCTGGCCTTGTGGTCCCCCTCCTGCTTGGGGCCACCCTGACCTACACATACCGCCACTGCTGGCCTCACAAGCCCCTGGTTACTGCAGATGAAGCTGGGATGGAGGCTCTGACCCCACCACCGGCCACCCATCTGTCACCCTTGGACAGCGCCCACACCCTTCTAGCACCTCCTGACAGCAGTGAGAAGATCTGCACCGTCCAGTTGGTGGGTAACAGCTGGACCCCTGGCTACCCCGAGACCCAGGAGGCGCTCTGCCCGCAGGTGACATGGTCCTGGGACCAGTTGCCCAGCAGAGCTCTTGGCCCCGCTGCTGCGCCCACACTCTCGCCAGAGTCCCCAGCCGGCTCGCCAGCCATGATGCTGCAGCCGGGCCCGCAGCTCTACGACGTGATGGACGCGGTCCCAGCGCGGCGCTGGAAGGAGTTCGTGCGCACGCTGGGGCTGCGCGAGGCAGAGATCGAAGCCGTGGAGGTGGAGATCGGCCGCTTCCGAGACCAGCAGTACGAGATGCTCAAGCGCTGGCGCCAGCAGCAGCCCGCGGGCCTCGGAGCCGTTTACGCGGCCCTGGAGCGCATGGGGCTGGACGGCTGCGTGGAAGACTTGCGCAGCCGCCTGCAGCGCGGCCCGTGACACGGCGCCCACTTGCCACCTAGGCGCTCTGGTGGCCCTTGCAGAAGCCCTAAGTACGGTTACTTATGCGTGTAGACATTTTATGTCACTTATTAAGCCGCTGGCACGGCCCTGCGTAGCAGCACCAGCCGGCCCCACCCCTGCTCGCCCCTATCGCTCCAGCCAAGGCGAAGAAGCACGAACGAATGTCGAGAGGGGGTGAAGACATTTCTCAACTTCTCGGCCGGAGTTTGGCTGAGATCGCGGTATTAAATCTGTGAAAGAAAACAAAACAAAACAAAAACGGCTTCTTGGCGTTTCTGCGGGGCTGGGGTGTTAAGTGGACTGGACTTTTCTCGAGGGATTCGAAGGGGACGGGAATCTTGTCACCCCGGGATCTGGCACCCATGGTGGAGTCCAGTGTGGCCTTAGCTCCCAAGCCTGCCCCTCCCGAGTCCACTCTGGCTCAATTACCCCGAGAAGGAGAGAGCAAGTCGCGGCCACAGCGAGTGAGTGAACCGGAGCCCAGATGAGAGCGCTTTAATGGGGCTGCGAGGTGGCGGAGACAGGGTCGGGATGGGGTGCAGCAGTTGGAGACACAGGGTCAGGGCCCCTCATCCTCTATTCACTCCACCGGGGCAGTGAAAGGGTCCCGGCAGCGAGTGGGTC (SEQ ID NO: 175) >NP_003781.1 tumor necrosis factor receptorsuperfamily member 25 isoform 2 precursor [Homo sapiens]MEQRPRGCAAVAAALLLVLLGARAQGGTRSPRCDCAGDFHKKIGLFCCRGCPAGHYLKAPCTEPCGNSTCLVCPQDTFLAWENHHNSECARCQACDEQASQVALENCSAVADTRCGCKPGWFVECQVSQCVSSSPFYCQPCLDCGALHRHTRLLCSRRDTDCGTCLPGFYEHGDGCVSCPTSTLGSCPERCAAVCGWRQMFWVQVLLAGLVVPLLLGATLTYTYRHCWPHKPLVTADEAGMEALTPPPATHLSPLDSAHTLLAPPDSSEKICTVQLVGNSWTPGYPETQEALCPQVTWSWDQLPSRALGPAAAPTLSPESPAGSPAMMLQPGPQLYDVMDAVPARRWKEFVRTLGLREAEIEAVEVEIGRFRDQQYEMLKRWRQQQPAGLGAVYAALERMGLDGCVEDLRSRLQRGP (SEQ ID NO: 176)Mouse DR3 >NM_033042.4 Mus musculus tumor necrosis factorreceptor superfamily, member 25 (Tnfrsf25), transcript variant 2, mRNACTGCGTGGAGGGGAAATGGGCCAGAGGCTGCTGGCAGGGGGCCTCCTCTGCTGTACACAAGCTGGTTTTGTAGACAGTGAGAGGGAAGCTGATCCCAGTCCCCTAACCCTGTTCTGCCCAGGAGCCTGAGAACTGAGCTTACTCGGGCAAATGCTAGGGCTTCAGAAATGGAGGAGCTGCCTAGGAGGGAGAGGTCACCTCCTGGGGCAGCCACACCAGGGTCAACTGCACGTGTTCTCCAGCCTCTGTTCCTACCACTGCTGCTGCTGCTGCTGCTGCTGCTTGGTGGCCAGGGCCAGGGCGGCATGTCTGGCAGGTGTGACTGTGCCAGTGAGTCCCAGAAGAGGTATGGCCCGTTTTGTTGCAGGGGCTGCCCAAAGGGACACTACATGAAGGCCCCCTGCGCAGAACCCTGTGGCAACTCCACCTGCCTTCCCTGTCCCTCGGACACCTTCTTGACCAGAGACAACCACTTTAAGACTGACTGTACCCGCTGCCAAGTCTGTGATGAAGAGGCCCTTCAAGTGACCCTTGAGAACTGCTCGGCAAAGTCGGACACCCACTGTGGCTGCCAGTCAGGCTGGTGTGTTGACTGCTCCACCGAGCCATGTGGGAAAAGCTCACCTTTCTCTTGTGTCCCATGCGGGGCTACAACACCAGTCCATGAGGCTCCAACCCCCCTGTTTTGGGTCCAGGTGCTTCTAGGAGTCGCGTTCCTTTTTGGGGCTATCCTGATCTGTGCATATTGTCGATGGCAGCCTTGTAAGGCCGTGGTCACTGCAGACACAGCTGGGACGGAGACCCTGGCCTCACCACAGACTGCCCATCTCTCAGCCTCAGACAGCGCCCACACCCTCCTGGCACCTCCAAGCAGTACTGGGAAAATCTGTACCACTGTOCAGTTGGTAGGCAACAACTGGACCCCTGGCTTATCCCAGACTCAGGAGGTGGTCTGCGGACAGGCCTCACAACCCTGGGATCAGCTGCCAAACAGAACTCTTGGAACTCCTCTGGCATCTCCGCTCTCGCCAGCGCCCCCTGCGGGCTCTCCGGCTGCTGTGCTCCAGCCTGGCCCGCAGCTCTACGATGTGATGGATGCGGTCCCAGCACGAAGGTGGAAGGAGTTCGTGCGCACGCTGGGGCTGCGGGAAGCGGAAATTGAAGCCGTGGAGGTGGAAATCTGCCGCTTCCGAGACCAGCAGTATGAGATGCTCAAGCGCTGGCGTCAGCAGCAGCCTGCAGGCCTCGGTGCCATCTATGCGGCTCTGGAGCGCATGGGTCTGGAAGGCTGTGCCGAGGACCTGCGCAGCCGCCTGCAGCGTGGCCCGTGATGGAAGGTCCATCAGCCACTTTGACACCCTAGTGACCCTTGAAGGAGCCTTAAGTATTGTTACTTATGCGTGTAGACATTTTATGTCAATTACTAACCCCCTGCCGTGGTCCTGCGTAGCAGGGCTGGCTGCCTCACTTTTGCTTATCTGCAGCACGGAGCTCCTGCTAAGGGAAGCGTCATGGAGAAATACCAGAAGGGGCCAAGTGATTGGTTGCTCAGCTGTTAATTAGCCCGAGTTTGGACTTGGTATTAAATTTCGTAAGAAAAGCAGCTGCTTG (SEQ ID NO: 177) >NP_149031.2 tumor necrosis factor receptorsuperfamily member 25 isoform 2 precursor [Mus musculus]MEELPRRERSPPGAATPGSTARVLQPLFLPLLLLLLLLLGGQGQGGMSGRCDCASESQKRYGPFCCRGCPKGHYMKAPCAEPCGNSTCLPCPSDTFLTRDNHFKTDCTRCQVCDEEALQVTLENCSAKSDTHCGCQSGWCVDCSTEPCGKSSPFSCVPCGATTPVHEAPTPLFWVQVLLGVAFLFGAILICAYCRWQPCKAVVTADTAGTETLASPQTAHLSASDSAHTLLAPPSSTGKICTTVQLVGNNWTPGLSQTQEVVCGQASQPWDQLPNRTLGTPLASPLSPAPPAGSPAAVLQPGPQLYDVMDAVPARRWKEFVRTLGLREAEIEAVEVEICRFRDQQYEMLKRWRQQQPAGLGAIYAALERMGLEGCAEDLRSRLQRGP (SEQ ID NO: 178) Human DcR3>NM_003823.4 Homo sapiens TNF receptor superfamilymember 6b (TNFRSF6B), mRNAGGACTTGGGCGGCCCCTCCGCAGGCGGACCGGGGGCAAAGGAGGTGGCATGTCGGTCAGGCACAGCAGGGTCCTGTGTCCGCGCTGAGCCGCGCTCTCCCTGCTCCAGCAAGGACCATGAGGGCGCTGGAGGGGCCAGGCCTGTCGCTGCTGTGCCTGGTGTTGGCGCTGCCTGCCCTGCTGCCGGTGCCGGCTGTACGCGGAGTGGCAGAAACACCCACCTACCCCTGGCGGGACGCAGAGACAGGGGAGCGGCTGGTGTGCGCCCAGTGCCCCCCAGGCACCTTTGTGCAGCGGCCGTGCCGCCGAGACAGCCCCACGACGTGTGGCCCGTGTCCACCGCGCCACTACACGCAGTTCTGGAACTACCTAGAGCGCTGCCGCTACTGCAACGTCCTCTGCGGGGAGCGTGAGGAGGAGGCACGGGCTTGCCACGCCACCCACAACCGTGCCTGCCGCTGCCGCACCGGCTTCTTCGCGCACGCTGGTTTCTGCTTGGAGCACGCATCGTGTCCACCTGGTGCCGGCGTGATTGCCCCGGGCACCCCCAGCCAGAACACGCAGTGCCAGCCGTGCCCCCCAGGCACCTTCTCAGCCAGCAGCTCCAGCTCAGAGCAGTGCCAGCCCCACCGCAACTGCACGGCCCTGGGCCTGGCCCTCAATGTGCCAGGCTCTTCCTCCCATGACACCCTGTGCACCAGCTGCACTGGCTTCCCCCTCAGCACCAGGGTACCAGGAGCTGAGGAGTGTGAGCGTGCCGTCATCGACTTTGTGGCTTTCCAGGACATCTCCATCAAGAGGCTGCAGCGGCTGCTGCAGGCCCTCGAGGCCCCGGAGGGCTGGGGTCCGACACCAAGGGCGGGCCGCGCGGCCTTGCAGCTGAAGCTGCGTCGGCGGCTCACGGAGCTCCTGGGGGCGCAGGACGGGGCGCTGCTGGTGCGGCTGCTGCAGGCGCTGCGCGTGGCCAGGATGCCCGGGCTGGAGCGGAGCGTCCGTGAGCGCTTCCTCCCTGTGCACTGATCCTGGCCCCCTCTTATTTATTCTACATCCTTGGCACCCCACTTGCACTGAAAGAGGCTTTTTTTTAAATAGAAGAAATGAGGTTTCTTAAAGCTTATTTTTATAAAGCTTTTTCATAAAA (SEQ ID NO: 179) >NP_003814.1 tumor necrosis factor receptorsuperfamily member 6B precursor [Homo sapiens]MRALEGPGLSLLCLVLALPALLPVPAVRGVAETPTYPWRDAETGERLVCAQCPPGTFVQRPCRRDSPTTCGPCPPRHYTQFWNYLERCRYCNVLCGEREEEARACHATHNRACRCRTGFFAHAGFCLEHASCPPGAGVIAPGTPSQNTQCQPCPPGTFSASSSSSEQCQPHRNCTALGLALNVPGSSSHDTLCTSCTGFPLSTRVPGAEECERAVIDFVAFQDISIKRLQRLLQALEAPEGWGPTPRAGRAALQLKLRRRLTELLGAQDGALLVRLLQALRVARMPGLERSVRERFLPVH (SEQ ID NO: 180) Human FasL>NM_000639.3 Homo sapiens Fas ligand (FASLG), transcript variant 1, mRNAAGCAGTCAGCAACAGGGTCCCGTCCTTGACACCTCAGCCTCTACAGGACTGAGAAGAAGTAAAACCGTTTGCTGGGGCTGGCCTGACTCACCAGCTGCCATGCAGCAGCCCTTCAATTACCCATATCCCCAGATCTACTGGGTGGACAGCAGTGCCAGCTCTCCCTGGGCCCCTCCAGGCACAGTTCTTCCCTGTCCAACCTCTGTGCCCAGAAGGCCTGGTCAAAGGAGGCCACCACCACCACCGCCACCGCCACCACTACCACCTCCGCCGCCGCCGCCACCACTGCCTCCACTACCGCTGCCACCCCTGAAGAAGAGAGGGAACCACAGCACAGGCCTGTGTCTCCTTGTGATGTTTTTCATGGTTCTGGTTGCCTTGGTAGGATTGGGCCTGGGGATGTTTCAGCTCTTCCACCTACAGAAGGAGCTGGCAGAACTCCGAGAGTCTACCAGCCAGATGCACACAGCATCATCTTTGGAGAAGCAAATAGGCCACCCCAGTCCACCCCCTGAAAAAAAGGAGCTGAGGAAAGTGGCCCATTTAACAGGCAAGTCCAACTCAAGGTCCATGCCTCTGGAATGGGAAGACACCTATGGAATTGTCCTGCTTTCTGGAGTGAAGTATAAGAAGGGTGGCCTTGTGATCAATGAAACTGGGCTGTACTTTGTATATTCCAAAGTATACTTCCGGGGTCAATCTTGCAACAACCTGCCCCTGAGCCACAAGGTCTACATGAGGAACTCTAAGTATCCCCAGGATCTGGTGATGATGGAGGGGAAGATGATGAGCTACTGCACTACTGGGCAGATGTGGGCCCGCAGCAGCTACCTGGGGGCAGTGTTCAATCTTACCAGTGCTGATCATTTATATGTCAACGTATCTGAGCTCTCTCTGGTCAATTTTGAGGAATCTCAGACGTTTTTCGGCTTATATAAGCTCTAAGAGAAGCACTTTGGGATTCTTTCCATTATGATTCTTTGTTACAGGCACCGAGAATGTTGTATTCAGTGAGGGTCTTCTTACATGCATTTGAGGTCAAGTAAGAAGACATGAACCAAGTGGACCTTGAGACCACAGGGTTCAAAATGTCTGTAGCTCCTCAACTCACCTAATGTTTATGAGCCAGACAAATGGAGGAATATGACGGAAGAACATAGAACTCTGGGCTGCCATGTGAAGAGGGAGAAGCATGAAAAAGCAGCTACCAGGTGTTCTACACTCATCTTAGTGCCTGAGAGTATTTAGGCAGATTGAAAAGGACACCTTTTAACTCACCTCTCAAGGTGGGCCTTGCTACCTCAAGGGGGACTGTCTTTCAGATACATGGTTGTGACCTGAGGATTTAAGGGATGGAAAAGGAAGACTAGAGGCTTGCATAATAAGCTAAAGAGGCTGAAAGAGGCCAATGCCCCACTGGCAGCATCTTCACTTCTAAATGCATATCCTGAGCCATCGGTGAAACTAACAGATAAGCAAGAGAGATGTTTTGGGGACTCATTTCATTCCTAACACAGCATGTGTATTTCCAGTGCAATTGTAGGGGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTATGACTAAAGAGAGAATGTAGATATTGTGAAGTACATATTAGGAAAATATGGGTTGCATTTGGTCAAGATTTTGAATGCTTCCTGACAATCAACTCTAATAGTGCTTAAAAATCATTGATTGTCAGCTACTAATGATGTTTTCCTATAATATAATAAATATTTATGTAGATGTGCATTTTTGTGAAATGAAAACATGTAATAAAAAGTATATGTTAGGATACAAATAA (SEQ ID NO: 181) >NP_000630.1 tumor necrosis factor ligand superfamilymember 6 isoform 1 [Homo sapiens]MQQPFNYPYPQIYWVDSSASSPWAPPGTVLPCPTSVPRRPGQRRPPPPPPPPPLPPPPPPPPLPPLPLPPLKKRGNHSTGLCLLVMFFMVLVALVGLGLGMFQLFHLQKELAELRESTSQMHTASSLEKQIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGGLVINETGLYFVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWARSSYLGAVFNLTSADHLYVNVSELSLVNFEESQTFFGLYKL (SEQ ID NO: 182) Mouse FasL>NM_010177.4 Mus musculus Fas ligand (TNFsuperfamily, member 6) (Fasl), transcript variant 1, mRNATGAGGCTTCTCAGCTTCAGATGCAAGTGAGTGGGTGTCTCACAGAGAAGCAAAGAGAAGAGAACAGGAGAAAGGTGTTTCCCTTGACTGCGGAAACTTTATAAAGAAAACTTAGCTTCTCTGGAGCAGTCAGCGTCAGAGTTCTGTCCTTGACACCTGAGTCTCCTCCACAAGGCTGTGAGAAGGAAACCCTTTCCTGGGGCTGGGTGCCATGCAGCAGCCCATGAATTACCCATGTCCCCAGATCTTCTGGGTAGACAGCAGTGCCACTTCATCTTGGGCTCCTCCAGGGTCAGTTTTTCCCTGTCCATCTTGTGGGCCTAGAGGGCCGGACCAAAGGAGACCGCCACCTCCACCACCACCTGTGTCACCACTACCACCGCCATCACAACCACTCCCACTGCCGCCACTGACCCCTCTAAAGAAGAAGGACCACAACACAAATCTGTGGCTACCGGTGGTATTTTTCATGGTTCTGGTGGCTCTGGTTGGAATGGGATTAGGAATGTATCAGCTCTTCCACCTGCAGAAGGAACTGGCAGAACTCCGTGAGTTCACCAACCAAAGCCTTAAAGTATCATCTTTTGAAAAGCAAATAGCCAACCCCAGTACACCCTCTGAAAAAAAAGAGCCGAGGAGTGTGGCCCATTTAACAGGGAACCCCCACTCAAGGTCCATCCCTCTGGAATGGGAAGACACATATGGAACCGCTCTGATCTCTGGAGTGAAGTATAAGAAAGGTGGCCTTGTGATCAACGAAACTGGGTTGTACTTCGTGTATTCCAAAGTATACTTCCGGGGTCAGTCTTGCAACAACCAGCCCCTAAACCACAAGGTCTATATGAGGAACTCTAAGTATCCTGAGGATCTGGTGCTAATGGAGGAGAAGAGGTTGAACTACTGCACTACTGGACAGATATGGGCCCACAGCAGCTACCTGGGGGCAGTATTCAATCTTACCAGTGCTGACCATTTATATGTCAACATATCTCAACTCTCTCTGATCAATTTTGAGGAATCTAAGACCTTTTTCGGCTTGTATAAGCTTTAAAAGAAAAAGCATTTTAAAATGATCTACTATTCTTTATCATGGGCACCAGGAATATTGTCTTGAATGAGAGTCTTCTTAAGACCTATTGAGATTAATTAAGACTACATGAGCCACAAAGACCTCATGACCGCAAGGTCCAACAGGTCAGCTATCCTTCATTTTCTCGAGGTCCATGGAGTGGTCCTTAATGCCTGCATCATGAGCCAGATGGAAGGAGGTCTGTGACTGAGGGACATAAAGCTTTGGGCTGCTGTGTGACAATGCAGAGGCACAGAGAAAGAACTGTCTGATGTTAAATGGCCAAGAGAATTTTAACCATTGAAGAAGACACCTTTACACTCACTTCCAGGGTGGGTCTACTTACTACCTCACAGAGGCCGTTTTTGAGACATAGTTGTGGTATGAATATACAAGGGTGAGAAAGGAGGCTCATTTGACTGATAAGCTAGAGACTGAAAAAAAGACAGTGTCTCATTGGCACCATCTTTACTGTTACCTAATGTTTTCTGAGCCGACCTTTGATCCTAACGGAGAAGTAAGAGGGATGTTTGAGGCACAAATCATTCTCTACATAGCATGCATACCTCCAGTGCAATGATGTCTGTGTGTTTGTATGTATGAGAGCAAACAGATTCTAAGGAGTCATATAAATAAAATATGTACATTATGGAGTACATATTAGAAACCTGTTACATTTGATGCTAGATATCTGAATGTTTCTTGGCAATAAACTCTAATAGTCTTCAAAATCTTTTATTATCAGCTACTGATGCTGTTTTTCTTTAATACAACTAGTATTTATGCTCTGAACATCCTAATGAGGAAAAGACAAATAAAATTATGTTATAGAATACAGAAATGCCTTAAGGACATAGACTTTGGAAA (SEQ ID NO: 183) >NP_034307.1 tumor necrosis factor ligand superfamilymember 6 isoform 1 [Mus musculus]MQQPMNYPCPQIFWVDSSATSSWAPPGSVFPCPSCGPRGPDQRRPPPPPPPVSPLPPPSQPLPLPPLTPLKKKDHNTNLWLPVVFFMVLVALVGMGLGMYQLFHLQKELAELREFTNQSLKVSSFEKQIANPSTPSEKKEPRSVAHLTGNPHSRSIPLEWEDTYGTALISGVKYKKGGLVINETGLYFVYSKVYFRGQSCNNQPLNHKVYMRNSKYPEDLVLMEEKRLNYCTTGQIWAHSSYLGAVFNLTSADHLYVNISQLSLINFEESKTFFGLYKL (SEQ ID NO: 184) Human TIM-1>NM_012206.3 Homo sapiens hepatitis A virus cellular (CD365)receptor 1 (HAVCR1), transcript variant 1, mRNAGACCAGGAGTCAGTTTGGCGGTTATGTGTGGGGAAGAAGCTGGGAAGTCAGGGGCTGTTTCTGTGGACAGCTTTCCCTGTCCTTTGGAAGGCACAGAGCTCTCAGCTGCAGGGAACTAACAGAGCTCTGAAGCCGTTATATGTGGTCTTCTCTCATTTCCAGCAGAGCAGGCTCATATGAATCAACCAACTGGGTGAAAAGATAAGTTGCAATCTGAGATTTAAGACTTGATCAGATACCATCTGGTGGAGGGTACCAACCAGCCTGTCTGCTCATTTTCCTTCAGGCTGATCCCATAATGCATCCTCAAGTGGTCATCTTAAGCCTCATCCTACATCTGGCAGATTCTGTAGCTGGTTCTGTAAAGGTTGGTGGAGAGGCAGGTCCATCTGTCACACTACCCTGCCACTACAGTGGAGCTGTCACATCCATGTGCTGGAATAGAGGCTCATGTTCTCTATTCACATGCCAAAATGGCATTGTCTGGACCAATGGAACCCACGTCACCTATCGGAAGGACACACGCTATAAGCTATTGGGGGACCTTTCAAGAAGGGATGTCTCTTTGACCATAGAAAATACAGCTGTGTCTGACAGTGGCGTATATTGTTGCCGTGTTGAGCACCGTGGGTGGTTCAATGACATGAAAATCACCGTATCATTGGAGATTGTGCCACCCAAGGTCACGACTACTCCAATTGTCACAACTGTTCCAACCGTCACGACTGTTCGAACGAGCACCACTGTTCCAACGACAACGACTGTTCCAATGACGACTGTTCCAACGACAACTGTTCCAACAACAATGAGCATTCCAACGACAACGACTGTTCTGACGACAATGACTGTTTCAACGACAACGAGCGTTCCAACGACAACGAGCATTCCAACAACAACAAGTGTTCCAGTGACAACAACTGTCTCTACCTTTGTTCCTCCAATGCCTTTGCCCAGGCAGAACCATGAACCAGTAGCCACTTCACCATCTTCACCTCAGCCAGCAGAAACCCACCCTACGACACTGCAGGGAGCAATAAGGAGAGAACCCACCAGCTCACCATTGTACTCTTACACAACAGATGGGAATGACACCGTGACAGAGTCTTCAGATGGCCTTTGGAATAACAATCAAACTCAACTGTTCCTAGAACATAGTCTACTGACGGCCAATACCACTAAAGGAATCTATGCTGGAGTCTGTATTTCTGTCTTGGTGCTTCTTGCTCTTTTGGGTGTCATCATTGCCAAAAAGTATTTCTTCAAAAAGGAGGTTCAACAACTAAGTGTTTCATTTAGCAGCCTTCAAATTAAAGCTTTGCAAAATGCAGTTGAAAAGGAAGTCCAAGCAGAAGACAATATCTACATTGAGAATAGTCTTTATGCCACGGACTAAGACCCAGTGGTGCTCTTTGAGAGTTTACGCCCATGAGTGCAGAAGACTGAACAGACATCAGCACATCAGACGTCTTTTAGACCCCAAGACAATTTTTCTGTTTCAGTTTCATCTGGCATTCCAACATGTCAGTGATACTGGGTAGAGTAACTCTCTCACTCCAAACTGTGTATAGTCAACCTCATCATTAATGTAGTCCTAATTTTTTATGCTAAAACTGGCTCAATCCTTCTGATCATTGCAGTTTTCTCTCAAATATGAACACTTTATAATTGTATGTTCTTTTTAGACCCCATAAATCCTGTATACATCAAAGAGAA (SEQ ID NO: 185) >NP_036338.2 hepatitis A virus cellular receptor 1isoform a precursor [Homo sapiens]MHPQVVILSLILHLADSVAGSVKVGGEAGPSVTLPCHYSGAVTSMCWNRGSCSLFTCQNGIVWTNGTHVTYRKDTRYKLLGDLSRRDVSLTIENTAVSDSGVYCCRVEHRGWFNDMKITVSLEIVPPKVTTTPIVTTVPTVTTVRTSTTVPTTTTVPMTTVPTTTVPTTMSIPTTTTVLTTMTVSTTTSVPTTTSIPTTTSVPVTTTVSTFVPPMPLPRQNHEPVATSPSSPQPAETHPTTLQGAIRREPTSSPLYSYTTDGNDTVTESSDGLWNNNQTQLFLEHSLLTANTTKGIYAGVCISVLVLLALLGVIIAKKYFFKKEVQQLSVSFSSLQIKALQNAVEKEVQAEDNIYIENSLYATD (SEQ ID NO: 186)Mouse TIM-1 >NM_134248.2 Mus musculus hepatitis A virus cellularreceptor 1 (Havcr1), transcript variant 1, mRNAGTCAGTACCATGAATCAGATTCAAGTCTTCATTTCAGGCCTCATACTGCTTCTCCCAGGCGCTGTGGATTCTTATGTGGAAGTAAAGGGGGTGGTGGGTCACCCTGTCACACTTCCATGTACTTACTCAACATATCGTGGAATCACAACGACATGTTGGGGCCGAGGGCAATGCCCATCTTCTGCTTGTCAAAATACACTTATTTGGACCAATGGACATCGTGTCACCTATCAGAAGAGCAGTCGGTACAACTTAAAGGGGCATATTTCAGAAGGAGATGTGTCCTTGACGATAGAGAACTCTGTTGAGAGTGACAGTGOTCTGTATTGTTGTCGAGTGGAGATTOCTGOATGGTTTAATGATCAGAAAGTGACCTTTTCATTGCAAGTTAAACCAGAGATTCCCACACGTCCTCCAAGAAGACCCACAACTACAAGGCCCACAGCTACAGGAAGACCCACGACTATTTCAACAAGATCCACACATGTACCAACATCAACCAGAGTCTCTACCTCCACTCCTCCAACATCTACACACACATGGACTCACAAACCAGAACCCACTACATTTTGTCCCCATGAGACAACAGCTGAGGTGACAGGAATCCCATCCCATACTCCTACAGACTGGAATGGCACTGTGACATCCTCAGGAGATACCTGGAGTAATCACACTGAAGCAATCCCTCCAGGGAAGCCGCAGAAAAACCCTACTAAGGGCTTCTATGTTGGCATCTGCATCGCAGCCCTGCTGCTACTGCTCCTTGTGAGCACCGTGGCTATCACCAGGTACATACTTATGAAAAGGAAGTCAGCATCTCTAAGCGTGGTTGCCTTCCGTGTCTCTAAGATTGAAGCTTTGCAGAACGCAGCGGTTGTGCATTCCCGAGCTGAAGACAACATCTACATTGTTGAAGATAGACCTTGAGGGGCAGAATGAGTACCAGTGGCCCTCTGAGGGACCTTCTGCCTGAGATTTATAGAGACTGTCACTGATGTCATAGAGTCACACCCATTACAGCGCCAAGGCGATTTTCTGTGTTGGTTCTTCCAGCTGCAGCAGAGAGGGTAACCCTCTACTGTGTATACTCAAAACTCAGATTAACATCATCCTAATTTTGGTATCTGCACCACCTCCGTGTCTCTGCTCACTACAGAGATTCTCTCAAACATGAACGTTTTAGAAGTTTGTGTTTCCCTTAGTCAATGTAATCATTGGTAATACTATTCTATTCTTGGTTACTAAAACCATTACTAAGAGAGGGATAGGAATTAAAAGTTGGTGTGAGGGGCCTCCTGAATTTAGAAGCACTTGATTCTGTTTTATCTACTTTCTTGAAATGTTACTTCTACCCTTCCCAATGGGTAAAATCATGGGAGCATGGTGCCCTCATAGATAAATAGAAGAGAGTCTATTGCTGCCAATATAGATGGTTATGCTTTCTCATAGCTCTGAAAATATGACACATTTATTATGAGGTTGATCTTAGGATAAGGATAGGTGTTTTATGTCAGGAGAGGTTATCATGGTGAATATGGACCAGCAGACAGCAGTGGAGGAAAATAATGAACCAAGGGATTGAGTTCATTAGTGCTAATTCTACTCCACTCCTGTCTTTATGCTCCTAAACTTACTGACTGAGCTCTGAATTAGGTGCTAGGAGGAGACAATGCAGACATGAAAGGGGAAGGAGCGCCTTCAGGACACAGGCTCTCTGCTGAGAGAAGTCCTATTTGCAGGTGTGATAGAGGTTGGGACAATCTCTGAGTTGTAAATTTCTAATTGTCTTCAGGCCATATTTATAGTTAAATTCATTTCCGAAAGACATAGCATCTTCCCCAATGGGTCAGTTTGTCAAAATCAATAAAATATTTTGTTTTGCTAAGAATTAAAAAAAAAAAAAAAAAAA (SEQ ID NO: 187) >NP_599009.2 hepatitis A virus cellular receptor 1homolog isoform a precursor [Mus musculus]MNQIQVFISGLILLLPGAVDSYVEVKGVVGHPVTLPCTYSTYRGITTTCWGRGQCPSSACQNTLIWTNGHRVTYQKSSRYNLKGHISEGDVSLTIENSVESDSGLYCCRVEIPGWFNDQKVTFSLQVKPEIPTRPPRRPTTTRPTATGRPTTISTRSTHVPTSTRVSTSTPPTSTHTWTHKPEPTTFCPHETTAEVTGIPSHTPTDWNGTVTSSGDTWSNHTEAIPPGKPQKNPTKGFYVGICIAALLLLLLVSTVAITRYILMKRKSASLSVVAFRVSKIEALQNAAVVHSRAEDNIYIVEDRP (SEQ ID NO: 188) Human PD-1>NM_005018.3 Homo sapiens programmed cell death 1 (PDCD1), mRNAGCTCACCTCCGCCTGAGCAGTGGAGAAGGCGGCACTCTGGTGGGGCTGCTCCAGGCATGCAGATCCCACAGGCGCCCTGGCCAGTCGTCTGGGCGGTGCTACAACTGGGCTGGCGGCCAGGATGGTTCTTAGACTCCCCAGACAGGCCCTGGAACCCCCCCACCTTCTCCCCAGCCCTGCTCGTGGTGACCGAAGGGGACAACGCCACCTTCACCTGCAGCTTCTCCAACACATCGGAGAGCTTCGTGCTAAACTGGTACCGCATGAGCCCCAGCAACCAGACGGACAAGCTGGCCGCCTTCCCCGAGGACCGCAGCCAGCCCGGCCAGGACTGCCGCTTCCGTGTCACACAACTGCCCAACGGGCGTGACTTCCACATGAGCGTGGTCAGGGCCCGGCGCAATGACAGCGGCACCTACCTCTGTGGGGCCATCTCCCTGGCCCCCAAGGCGCAGATCAAAGAGAGCCTGCGGGCAGAGCTCAGGGTGACAGAGAGAAGGGCAGAAGTGCCCACAGCCCACCCCAGCCCCTCACCCAGGCCAGCCGGCCAGTTCCAAACCCTGGTGGTTGGTGTCGTGGGCGGCCTGCTGGGCAGCCTGGTGCTGCTAGTCTGGGTCCTGGCCGTCATCTGCTCCCGGGCCGCACGAGGGACAATAGGAGCCAGGCGCACCGGCCAGCCCCTGAAGGAGGACCCCTCAGCCGTGCCTGTGTTCTCTGTGGACTATGGGGAGCTGGATTTCCAGTGGCGAGAGAAGACCCCGGAGCCCCCCGTGCCCTGTGTCCCTGAGCAGACGGAGTATGCCACCATTGTCTTTCCTAGCGGAATGGGCACCTCATCCCCCGCCCGCAGGGGCTCAGCTGACGGCCCTCGGAGTGCCCAGCCACTGAGGCCTGAGGATGGACACTGCTCTTGGCCCCTCTGACCGGCTTCCTTGGCCACCAGTGTTCTGCAGACCCTCCACCATGAGCCCGGGTCAGCGCATTTCCTCAGGAGAAGCAGGCAGGGTGCAGGCCATTGCAGGCCGTCCAGGGGCTGAGCTGCCTGGGGGCGACCGGGGCTCCAGCCTGCACCTGCACCAGGCACAGCCCCACCACAGGACTCATGTCTCAATGCCCACAGTGAGCCCAGGCAGCAGGTGTCACCGTCCCCTACAGGGAGGGCCAGATGCAGTCACTGCTTCAGGTCCTGCCAGCACAGAGCTGCCTGCGTCCAGCTCCCTGAATCTCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCCTGCGGCCCGGGGCTGAAGGCGCCGTGGCCCTGCCTGACGCCCCGGAGCCTCCTGCCTGAACTTGGGGGCTGGTTGGAGATGGCCTTGGAGCAGCCAAGGTGCCCCTGGCAGTGGCATCCCGAAACGCCCTGGACGCAGGGCCCAAGACTGGGCACAGGAGTGGGAGGTACATGGGGCTGGGGACTCCCCAGGAGTTATCTGCTCCCTGCAGGCCTAGAGAAGTTTCAGGGAAGGTCAGAAGAGCTCCTGGCTGTGGTGGGCAGGGCAGGAAACCCCTCCACCTTTACACATGCCCAGGCAGCACCTCAGGCCCTTTGTGGGGCAGGGAAGCTGAGGCAGTAAGCGGGCAGGCAGAGCTGGAGGCCTTTCAGGCCCAGCCAGCACTCTGGCCTCCTGCCGCCGCATTCCACCCCAGCCCCTCACACCACTCGGGAGAGGGACATCCTACGGTCCCAAGGTCAGGAGGGCAGGGCTGGGGTTGACTCAGGCCCCTCCCAGCTGTGGCCACCTGGGTGTTGGGAGGGCAGAAGTGCAGGCACCTAGGGCCCCCCATGTGCCCACCCTGGGAGCTCTCCTTGGAACCCATTCCTGAAATTATTTAAAGGGGTTGGCCGGGCTCCCACCAGGGCCTGGGTGGGAAGGTACAGGCGTTCCCCCGGGGCCTAGTACCCCCGCCGTGGCCTATCCACTCCTCACATCCACACACTGCACCCCCACTCCTGGGGCAGGGCCACCAGCATCCAGGCGGCCAGCAGGCACCTGAGTGGCTGGGACAAGGGATCCCCCTTCCCTGTGGTTCTATTATATTATAATTATAATTAAATATGAGAGCATGCTAA (SEQ ID NO: 189) >NP_005009.2 programmed cell death protein 1precursor [Homo sapiens]MQIPQAPWPVVWAVLQLGWRPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVVGVVGGLLGSLVLLVWVLAVICSRAARGTIGARRTGQPLKEDPSAVPVFSVDYGELDFQWREKTPEPPVPCVPEQTEYATIVFPSGMGTSSPARRGSADGPRSAQPLRPEDGHCSWPL (SEQ ID NO: 190) Mouse PD-1>NM_008798.3 Mus musculus programmed cell death 1 (Pdcd1), mRNATGAGCAGCGGGGAGGAGGAAGAGGAGACTGCTACTGAAGGCGACACTGCCAGGGGCTCTGGGCATGTGGGTCCGGCAGGTACCCTGGTCATTCACTTGGGCTGTGCTGCAGTTGAGCTGGCAATCAGGGTGGCTTCTAGAGGTCCCCAATGGGCCCTGGAGGTCCCTCACCTTCTACCCAGCCTGGCTCACAGTGTCAGAGGGAGCAAATGCCACCTTCACCTGCAGCTTGTCCAACTGGTCGGAGGATCTTATGCTGAACTGGAACCGCCTGAGTCCCAGCAACCAGACTGAAAAACAGGCCGCCTTCTGTAATGGTTTGAGCCAACCCGTCCAGGATGCCCGCTTCCAGATCATACAGCTGCCCAACAGGCATGACTTCCACATGAACATCCTTGACACACGGCGCAATGACAGTGGCATCTACCTCTGTGGGGCCATCTCCCTGCACCCCAAGGCAAAAATCGAGGAGAGCCCTGGAGCAGAGCTCGTGGTAACAGAGAGAATCCTGGAGACCTCAACAAGATATCCCAGCCCCTCGCCCAAACCAGAAGGCCGGTTTCAAGGCATGGTCATTGGTATCATGAGTGCCCTAGTGGGTATCCCTGTATTGCTGCTGCTGGCCTGGGCCCTAGCTGTCTTCTGCTCAACAAGTATGTCAGAGGCCAGAGGAGCTGGAAGCAAGGACGACACTCTGAAGGAGGAGCCTTCAGCAGCACCTGTCCCTAGTGTGGCCTATGAGGAGCTGGACTTCCAGGGACGAGAGAAGACACCAGAGCTCCCTACCGCCTGTGTGCACACAGAATATGCCACCATTGTCTTCACTGAAGGGCTGGGTGCCTCGGCCATGGGACGTAGGGGCTCAGCTGATGGCCTGCAGGGTCCTCGGCCTCCAAGACATGAGGATGGACATTGTTCTTGGCCTCTTTGACCAGATTCTTCAGCCATTAGCATGCTGCAGACCCTCCACAGAGAGCACCGGTCCGTCCCTCAGTCAAGAGGAGCATGCAGGCTACAGTTCAGCCAAGGCTCCCAGGGTCTGAGCTAGCTGGAGTGACAGCCCAGCGCCTGCACCAATTCCAGCACATGCACTGTTGAGTGAGAGCTCACTTCAGGTTTACCACAAGCTGGGAGCAGCAGGCTTCCCGGTTTCCTATTGTCACAAGGTGCAGAGCTGGGGCCTAAGCCTATGTCTCCTGAATCCTACTGTTGGGCACTTCTAGGGACTTGAGACACTATAGCCAATGGCCTCTGTGGGTTCTGTGCCTGGAAATGGAGAGATCTGAGTACAGCCTGCTTTGAATGGCCCTGTGAGGCAACCCCAAAGCAAGGGGGTCCAGGTATACTATGGGCCCAGCACCTAAAGCCACCCTTGGGAGATGATACTCAGGTGGGAAATTCGTAGACTGGGGGACTGAACCAATCCCAAGATCTGGAAAAGTTTTGATGAAGACTTGAAAAGCTCCTAGCTTCGGGGGTCTGGGAAGCATGAGCACTTACCAGGCAAAAGCTCCGTGAGCGTATCTGCTGTCCTTCTGCATGCCCAGGTACCTCAGTTTTTTTCAACAGCAAGGAAACTAGGGCAATAAAGGGAACCAGCAGAGCTAGAGCCACCCACACATCCAGGGGGGCACTTGACTCTCCCTACTCCTCCTAGGAACCAAAAGGACAAAGTCCATGTTGACAGCAGGGAAGGAAAGGGGGATATAACCTTGACGCAAACCAACACTGGGGTGTTAGAATCTCCTCATTCACTCTGTCCTGGAGTTGGGTTCTGGCTCTCCTTCACACCTAGGACTCTGAAATGAGCAAGCACTTCAGACAGTCAGGGTAGCAAGAGTCTAGCTGTCTGGTGGGCACCCAAAATGACCAGGGCTTAAGTCCCTTTCCTTTGGTTTAAGCCCGTTATAATTAAATGGTACCAAAAGCTTTAA (SEQ ID NO: 191) >NP_032824.1 programmed cell death protein 1precursor [Mus musculus]MWVRQVPWSFTWAVLQLSWQSGWLLEVPNGPWRSLTFYPAWLTVSEGANATFTCSLSNWSEDLMLNWNRLSPSNQTEKQAAFCNGLSQPVQDARFQIIQLPNRHDFHMNILDTRRNDSGIYLCGAISLHPKAKIEESPGAELVVTERILETSTRYPSPSPKPEGRFQGMVIGIMSALVGIPVLLLLAWALAVFCSTSMSEARGAGSKDDTLKEEPSAAPVPSVAYEELDFQGREKTPELPTACVHTEYATIVFTEGLGASAMGRRGSADGLQGPRPPRHEDGHCSWPL (SEQ ID NO: 191)mScarlet >KY021423.1 Synthetic construct mScarlet gene,partial cds, mRNA ATGGTGAGCAAGGGCGAGGCAGTGATCAAGGAGTTCATGCGGTTCAAGGTGCACATGGAGGGCTCCATGAACGGCCACGAGTTCGAGATCGAGGGCGAGGGCGAGGGCCGCCCCTACGAGGGCACCCAGACCGCCAAGCTGAAGGTGACCAAGGGTGGCCCCCTGCCCTTCTCCTGGGACATCCTGTCCCCTCAGTTCATGTACGGCTCCAGGGCCTTCACCAAGCACCCCGCCGACATCCCCGACTACTATAAGCAGTCCTTCCCCGAGGGCTTCAAGTGGGAGCGCGTGATGAACTTCGAGGACGGCGGCGCCGTGACCGTGACCCAGGACACCTCCCTGGAGGACGGCACCCTGATCTACAAGGTGAAGCTCCGCGGCACCAACTTCCCTCCTGACGGCCCCGTAATGCAGAAGAAGACAATGGGCTGGGAAGCGTCCACCGAGCGGTTGTACCCCGAGGACGGCGTGCTGAAGGGCGACATTAAGATGGCCCTGCGCCTGAAGGACGGCGGCCGCTACCTGGCGGACTTCAAGACCACCTACAAGGCCAAGAAGCCCGTGCAGATGCCCGGCGCCTACAACGTCGACCGCAAGTTGGACATCACCTCCCACAACGAGGACTACACCGTGGTGGAACAGTACGAACGCTCCGAGGGCCGCCACTCCACCGGCGGCATGGACGAGCTGTACAAG (SEQ ID NO: 192) >APD76535.1 mScarlet, partial [synthetic construct]MVSKGEAVIKEFMRFKVHMEGSMNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFSWDILSPQFMYGSRAFTKHPADIPDYYKQSFPEGFKWERVMNFEDGGAVTVTQDTSLEDGTLIYKVKLRGTNFPPDGPVMQKKTMGWEASTERLYPEDGVLKGDIKMALRLKDGGRYLADFKTTYKAKKPVQMPGAYNVDRKLDITSHNEDYTVVEQYERSEGRHSTGGMDELYK (SEQ ID NO: 193)Nanoluciferase >JQ513379. 1 NanoLuc reporter vectorpNL1.1.CMV[Nluc/CMV], complete sequence, mRNAGGCCTAACTGGCCTCAATATTGGCCATTAGCCATATTATTCATTGGTTATATAGCATAAATCAATATTGGCTATTGGCCATTGCATACGTTGTATCTATATCATAATATGTACATTTATATTGGCTCATGTCCAATATGACCGCCATGTTGGCATTGATTATTGACTAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTCCGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTACGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACACCAATGGGCGTGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAATAACCCCGCCCCGTTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCGTTTAGTGAACCGTCAGATCACTAGAAGCTTTATTGCGGTAGTTTATCACAGTTAAATTGCTAACGCAGTCAGTGGGCCTCGGCGGCCAAGCTTGGCAATCCGGTACTGTTGGTAAAGCCACCATGGTCTTCACACTCGAAGATTTCGTTGGGGACTGGCGACAGACAGCCGGCTACAACCTGGACCAAGTCCTTGAACAGGGAGGTGTGTCCAGTTTGTTTCAGAATCTCGGGGTGTCCGTAACTCCGATCCAAAGGATTGTCCTGAGCGGTGAAAATGGGCTGAAGATCGACATCCATGTCATCATCCCGTATGAAGGTCTGAGCGGCGACCAAATGGGCCAGATCGAAAAAATTTTTAAGGTGGTGTACCCTGTGGATGATCATCACTTTAAGGTGATCCTGCACTATGGCACACTGGTAATCGACGGGGTTACGCCGAACATGATCGACTATTTCGGACGGCCGTATGAAGGCATCGCCGTGTTCGACGGCAAAAAGATCACTGTAACAGGGACCCTGTGGAACGGCAACAAAATTATCGACGAGCGCCTGATCAACCCCGACGGCTCCCTGCTGTTCCGAGTAACCATCAACGGAGTGACCGGCTGGCGGCTGTGCGAACGCATTCTGGCGTAATTCTAGAGTCGGGGCGGCCGGCCGCTTCGAGCAGACATGATAAGATACATTGATGAGTTTGGACAAACCACAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAAATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGCTGCAATAAACAAGTTAACAACAACAATTGCATTCATTTTATGTTTCAGGTTCAGGGGGAGGTGTGGGAGGTTTTTTAAAGCAAGTAAAACCTCTACAAATGTGGTAAAATCGATAAGGATCCGTCGACCGATGCCCTTGAGAGCCTTCAACCCAGTCAGCTCCTTCCGGTGGGCGCGGGGCATGACTATCGTCGCCGCACTTATGACTGTCTTCTTTATCATGCAACTCGTAGGACAGGTGCCGGCAGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGATTATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAATCTAAAGTATATATGAGTAAACTTGGTCTGACAGCGGCCGCAAATGCTAAACCACTGCAGTGGTTACCAGTGCTTGATCAGTGAGGCACCGATCTCAGCGATCTGCCTATTTCGTTCGTCCATAGTGGCCTGACTCCCCGTCGTGTAGATCACTACGATTCGTGAGGGCTTACCATCAGGCCCCAGCGCAGCAATGATGCCGCGAGAGCCGCGTTCACCGGCCCCCGATTTGTCAGCAATGAACCAGCCAGCAGGGAGGGCCGAGCGAAGAAGTGGTCCTGCTACTTTGTCCGCCTCCATCCAGTCTATGAGCTGCTGTCGTGATGCTAGAGTAAGAAGTTCGCCAGTGAGTAGTTTCCGAAGAGTTGTGGCCATTGCTACTGGCATCGTGGTATCACGCTCGTCGTTCGGTATGGCTTCGTTCAACTCTGGTTCCCAGCGGTCAAGCCGGGTCACATGATCACCCATATTATGAAGAAATGCAGTCAGCTCCTTAGGGCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCGGTGTTGTCGCTCATGGTAATGGCAGCACTACACAATTCTCTTACCGTCATGCCATCCGTAAGATGCTTTTCCGTGACCGGCGAGTACTCAACCAAGTCGTTTTGTGAGTAGTGTATACGGCGACCAAGCTGCTCTTGCCCGGCGTCTATACGGGACAACACCGCGCCACATAGCAGTACTTTGAAAGTGCTCATCATCGGGAATCGTTCTTCGGGGCGGAAAGACTCAAGGATCTTGCCGCTATTGAGATCCAGTTCGATATAGCCCACTCTTGCACCCAGTTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCGGGGTGTGCAAAAACAGGCAAGCAAAATGCCGCAAAGAAGGGAATGAGTGCGACACGAAAATGTTGGATGCTCATACTCGTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTACTAGTACGTCTCTCAAGGATAAGTAAGTAATATTAAGGTACGGGAGGTATTGGACAGGCCGCAATAAAATATCTTTATTTTCATTACATCTGTGTGTTGGTTTTTTGTGTGAATCGATAGTACTAACATACGCTCTCCATCAAAACAAAACGAAACAAAACAAACTAGCAAAATAGGCTGTCCCCAGTGCAAGTGCAGGTGCCAGAACATTTCTCT (SEQ IDNO: 194) >AFJ15599.1 NanoLuc luciferase [NanoLuc reportervector pNL1.1.CMV[Nluc/CMV]]MVFTLEDFVGDWRQTAGYNLDQVLEQGGVSSLFQNLGVSVTPIQRIVLSGENGLKIDIHVIIPYEGLSGDQMGQIEKIFKVVYPVDDHHFKVILHYGTLVIDGVTPNMIDYFGRPYEGIAVFDGKKITVTGTLWNGNKIIDERLINPDGSLLFRVTINGVTGWRLCERILA (SEQ ID NO: 195)

The polypeptides provided in Table 1 above are involved in a range ofbiological processes, including but not limited to, suppressing theadaptive arm of the immune system (e.g., PD-L1); cellular adhesion(e.g., nectin), immune activation (e.g., HVEM), and the like. The POIdomains can also be used to track, purify, or identify the engineeredEVs from native EVs (e.g., mScarlet and nanoluciferase). The genes,transcripts, polypeptides, variants, and fragments thereof can be usedin any combination from Table 1 to be expressed by an engineered EVprovided herein. In some embodiments, the POI domain is the humanpolypeptide. In some embodiments, the POI domain is a homologue of thehuman polypeptide (e.g., mouse).

In some embodiments of any of the aspects, the engineered cell or EVprovided herein comprises an exogenous nucleic acid encoding one or moreexogenous polypeptide(s) selected from the group consisting of: thepolypeptides listed in Table 1.

In some embodiments of any of the aspects, the POI domain is PD-L1 or afragment thereof. In some embodiments of any of the aspects, the POIdomain is PD-L2 or a fragment thereof. In some embodiments of any of theaspects, the POI domain is FGL1 or a fragment thereof. In someembodiments of any of the aspects, the POI domain is 4-1BBL or afragment thereof. In some embodiments of any of the aspects, the POIdomain is CTLA or a fragment thereof.

In some embodiments of any of the aspects, the POI domain substantiallybinds to one or more of a target polypeptide. In some embodiments of anyof the aspects, the target polypeptide is a cellular receptor. In someembodiments of any of the aspects, the target polypeptide is animmunosuppressive polypeptide. In some embodiments of any of theaspects, the target polypeptide is an immunostimulatory polypeptide. Theengineered exosomes provided herein can be designed to activate, block,or modulate a given target polypeptide with the appropriate POI domainthat binds to or modulates the function or expression of the targetpolypeptide. Non-limiting examples of target polypeptides include thoselisted in Table 2 (below).

TABLE 2 Exemplary Target Polypeptides PD-1 VISTA LAG-3 CD44 CD80 BTLACD112 IL10RA CD86 CD160 CD200R IL10RB CD28 HVEM CD200 Tim-3 ICOS CD2Galectin 9 TNFRSF25 CD28H SLAM CD150 TIM-3 TNFRSF6B PD-Ll CD58 CD226CD113 CTLA-4 TIM-1 CD155 CD27 4-1BB (CD137) TIM-4 CD112 CD30 GITR CD40DR3 LFA-3 (CD58) CD27L CD30L GITRL CD40L CD48 CD244 DcR3 CD28H LFA-3(CD58) CD98 TNF Receptor TNF receptor Superfamily associated factormembers (TRAF) family members Butyrophilin family PD-L2 Nectin TIMfamily members members B7/CD28 family SLAM family Nectin-like Collagenmembers members binding receptors family proteins LAIR-1 (CD305)

The EVs provided herein further comprise at least one fusion proteincomprising a vesicle targeting domain. In various embodiments, thevesicle targeting domain provided herein is capable of binding oranchoring the fusion polypeptide provided herein to an extracellularvesicle, e.g., via targeting of the phospholipid bilayer membrane. Invarious embodiments, the vesicle targeting domain is a GPI domain (i.e.,GPI linker, GPI anchor), fatty acetylation site, or prenylation site.One of skill in the art can appreciate that the aforementioned refer topeptide or protein sites, wherein covalent lipid attachment supportsembedding of the lipid in a cell membrane (i.e., phospholipid bilayer).Biochemical forces that anchor EV targeting domains to the EVphospholipid bilayer may include, but are not limited to, electrostaticforces, affinity for EVs through protein-protein interactions withnatively resident proteins (e.g., CD81, CD63, CD9, ALIX, TSG101. CD98,CD298, MARCKS, PTGFRN, Lactadherin (MFGe8)), association or affinity fornegatively or positively curved phospholipids, association or affinityfor negatively or positively charged domains of resident membraneassociated proteins, etc., or the like.

Additional non-limiting examples of membrane targeting domains that canbe used and their properties are further described in detail, e.g.,Alberts B, Johnson A, Lewis J, et al., Molecular Biology of the Cell,4th edition, New York: Garland Science, 2002. Membrane Proteins,https://www.ncbi.nlm.nih.gov/books/NBK26878/; Marilyn D. Resh, Fattyacylation of proteins: new insights into membrane targeting ofmyristoylated and palmitoylated proteins. Biochimica et Biophysica Acta(BBA)—Molecular Cell Research. Volume 1451, Issue 1, 12 Aug. 1999, Pages1-16, doi.org/10.1016/S0167-4889(99)00075-0; Ann Apolloni, et. al.,H-ras but Not K-ras Traffics to the Plasma Membrane through the ExocyticPathway, Molecular and Cellular Biology April 2000, 20 (7) 2475-2487,DOI: 10.1128/MCB.20.7.2475-2487.2000; Rosie Dawaliby et. al.,Phosphatidylethanolamine Is a Key Regulator of Membrane Fluidity inEukaryotic Cells, Membrane Biology, VOLUME 291, ISSUE 7,doi.org/10.1074/jbc.M115.706523; R. J. Deschenes, ProteinPalmitoylation, Encyclopedia of Biological Chemistry (Second Edition),Academic Press, 2013, Pages 645-647, ISBN 9780123786319,https://doi.org/10.1016/B978-0-12-378630-2.00022-0.; Charuta C.Palsuledesai and Mark D. Distefano, Protein Prenylation: Enzymes,Therapeutics, and Biotechnology Applications, ACS Chemical Biology 201510 (1), 51-62, DOI: 10.1021/cb500791f; Hung M E, Leonard J N.Stabilization of exosome-targeting peptides via engineeredglycosylation, J Biol Chem, 2015 Mar. 27; 290(13):8166-72, doi:10.1074/jbc.M114.621383; Udenwobele Daniel Ikenna, et. al.,Myristoylation: An Important Protein Modification in the ImmuneResponse, Frontiers in Immunology, Vol:8, 2017,DOI=10.3389/fimmu.2017.00751; Kinoshita Taroh 2020 Biosynthesis andbiology of mammalian GPI-anchored proteins Open Biol. 10190290,http://doi.org/10.1098/rsob.190290, the contents of which areincorporated herein by reference in their entireties.

In some embodiments, the fusion polypeptide comprises one or more, twoor more, three or more, four or more, five or more, or six or morevesicle targeting domains on the same polypeptide or nucleic acidconstruct encoding said polypeptide. For example, the fusionpolypeptides provided herein can comprise PD-L1 andGlycosylphosphatidylinositol (GPI).

In some embodiments, the vesicle targeting domain is a prenylatedprotein. Prenylated proteins are proteins that have at least oneprenylation site. Prenylation occurs when a 15-carbon or 20-carbon,farnesyl or geranylgeranyl isoprenoid, respectively, is covalently boundvia a thioether bond to a cysteine at or near the carboxy terminus of aprotein. In general, a prenylation site comprises an amino acid sequenceCAAX, wherein C represents cysteine, A represents an aliphatic aminoacid (glycine, alanine, valine, leucine, or isoleucine), and Xrepresents alanine, methionine, serine, leucine, or glutamine.

In some embodiments, the vesicle targeting domain is a fatty acylatedprotein. Fatty acylated proteins are proteins that have been modifiedpost-translationally by covalent attachment of one or more fatty acids,generally with a saturated fatty acid that comprises 14-carbon (e.g.myristic acid) via myristoylation or 16-carbons (e.g. palmitic acid) viapalmitoylation. For example, proteins destined to become myristoylatedbegin with the amino acids Met-Gly-X-X-X followed by a serine orthreonine at position 6 and lysine or arginine at position 7 and/or 8wherein X can be any amino acid. The methionine is removed and amyristate is linked to the glycine via an amide bond. Palmitoylationherein means a posttranslational covalent attachment of fatty acids(e.g. palmitic acid) to cysteine (S-palmitoylation), serine and/orthreonine (0-palmitoylation), and to the amino group of lysine(N-palmitoylation) of proteins.

Palmitoylated proteins may be acylated by attachment of a thioesterlinkage to a sulfhydryl group of cysteine, or via a palmitate linked tothe amino group of an N-terminal cysteine. Palmitoylation sites may bepresent near the N- or C-terminus of a protein.

In some embodiments, the vesicle targeting domain is aglycosylphosphatidylinositol (GPI) anchor. Aglycosylphosphatidylinositol (GPI) anchor (“GPI anchor”) or “GPI stickybinder” are used interchangeably and refer to a means of stablyanchoring a protein to an outer leaflet (e.g. exterior layer of aphospholipid bilayer) of a cell membrane. A GPI anchor comprises aglycan, a phosphoethanolamine linker, a phospholipid tail, and may bemodified by various glycan sidechains. The glycan core comprisesphosphoinositol, glucosamine, and mannose residues wherein said mannoseresidues may be modified for example with phosphoethanolamine orcarbohydrates. The phosphoethanolamine is amide-bonded to the carboxylterminus of a protein during the process of GPI attachment. In someembodiments, the vesicle targeting domain may have affinity to EVresident proteins, e.g., CD81, CD63, CD9, ALIX, TSG101, CD98, CD298,MARCKS, PTGFRN, Lactadherin (MFGe8)

Sticky binders can include a sequence for one or more myristoylationand/or palmitoylation (Myr/Palm) sites fused to a transmembrane domainfrom 4F2 (CD98). For example, the myristoylation sequence from theMARCKS protein may be modified to encode for one or more myristoylationand palmitoylation sites, wherein the modified MARCKS protein sequenceis fused to a protein sequence of the transmembrane domain from 4F2 viaa covalent peptide bond. A Myr/Palm followed by the 4F2 transmembranedomain can improve loading of the fusion proteins provided herein whencompared with 4F2 transmembrane domain alone or Myr/Palm alone.

Non-limiting examples of vesicle targeting domains that enhance fusionpolypeptide structure and function on the extracellular vesicles areprovided in Table 3 (below).

TABLE 3 Exosome Targeting Domain Exosome Targeting Domain/StickyNucleic Acid Sequence (SEQ ID NO:) BinderAmino Acid Sequence (SEQ ID NO:) Human CD55>NM_000574.5 Homo sapiens CD55 molecule (Cromer blood (DAF)group) (CD55), transcript variant 1, mRNA GlycosylphosphatidylinositolCTGCTTACTGCAACTCGCTCCGGCCGCTGGGCGTAGCTGCGACTCGGCGGAGTCCCG (GPI)GCGGCGCGTCCTTGTTCTAACCCGGCGCGCCATGACCGTCGCGCGGCCGAGCGTGCCCGCGGCGCTGCCCCTCCTCGGGGAGCTGCCCCGGCTGCTGCTGCTGGTGCTGTTGTGCCTGCCGGCCGTGTGGGGTGACTGTGGCCTTCCCCCAGATGTACCTAATGCCCAGCCAGCTTTGGAAGGCCGTACAAGTTTTCCCGAGGATACTGTAATAACGTACAAATGTGAAGAAAGCTTTGTGAAAATTCCTGGCGAGAAGGACTCAGTGATCTGCCTTAAGGGCAGTCAATGGTCAGATATTGAAGAGTTCTGCAATCGTAGCTGCGAGGTGCCAACAAGGCTAAATTCTGCATCCCTCAAACAGCCTTATATCACTCAGAATTATTTTCCAGTCGGTACTGTTGTGGAATATGAGTGCCGTCCAGGTTACAGAAGAGAACCTTCTCTATCACCAAAACTAACTTGCCTTCAGAATTTAAAATGGTCCACAGCAGTCGAATTTTGTAAAAAGAAATCATGCCCTAATCCGGGAGAAATACGAAATGGTCAGATTGATGTACCAGGTGGCATATTATTTGGTGCAACCATCTCCTTCTCATGTAACACAGGGTACAAATTATTTGGCTCGACTTCTAGTTTTTGTCTTATTTCAGGCAGCTCTGTCCAGTGGAGTGACCCGTTGCCAGAGTGCAGAGAAATTTATTGTCCAGCACCACCACAAATTGACAATGGAATAATTCAAGGGGAACGTGACCATTATGGATATAGACAGTCTGTAACGTATGCATGTAATAAAGGATTCACCATGATTGGAGAGCACTCTATTTATTGTACTGTGAATAATGATGAAGGAGAGTGGAGTGGCCCACCACCTGAATGCAGAGGAAAATCTCTAACTTCCAAGGTCCCACCAACAGTTCAGAAACCTACCACAGTAAATGTTCCAACTACAGAAGTCTCACCAACTTCTCAGAAAACCACCACAAAAACCACCACACCAAATGCTCAAGCAACACGGAGTACACCTGTTTCCAGGACAACCAAGCATTTTCATGAAACAACCCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCAGACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAGCCAAAGAAGAGTTAAGAAGAAAATACACACAAGTATACAGACTGTTCCTAGTTTCTTAGACTTATCTGCATATTGGATAAAATAAATGCAATTGTGCTCTTCATTTAGGATGCTTTCATTGTCTTTAAGATGTGTTAGGAATGTCAACAGAGCAAGGAGAAAAAAGGCAGTCCTGGAATCACATTCTTAGCACACCTACACCTCTTGAAAATAGAACAACTTGCAGAATTGAGAGTGATTCCTTTCCTAAAAGTGTAAGAAAGCATAGAGATTTGTTCGTATTTAGAATGGGATCACGAGGAAAAGAGAAGGAAAGTGATTTTTTTCCACAAGATCTGTAATGTTATTTCCACTTATAAAGGAAATAAAAAATGAAAAACATTATTTGGATATCAAAAGCAAATAAAAACCCAATTCAGTCTCTTCTAAGCAAAATTGCTAAAGAGAGATGAACCACATTATAAAGTAATCTTTGGCTGTAAGGCATTTTCATCTTTCCTTCGGGTTGGCAAAATATTTTAAAGGTAAAACATGCTGGTGAACCAGGGGTGTTGATGGTGATAAGGGAGGAATATAGAATGAAAGACTGAATCTTCCTTTGTTGCACAAATAGAGTTTGGAAAAAGCCTGTGAAAGGTGTCTTCTTTGACTTAATGTCTTTAAAAGTATCCAGAGATACTACAATATTAACATAAGAAAAGATTATATATTATTTCTGAATCGAGATGTCCATAGTCAAATTTGTAAATCTTATTCTTTTGTAATATTTATTTATATTTATTTATGACAGTGAACATTCTGATTTTACATGTAAAACAAGAAAAGTTGAAGAAGATATGTGAAGAAAAATGTATTTTTCCTAAATAGAAATAAATGATCCCATTTTTTGGTATCATGTAGTATGTGAAATTTATTCTTAAACGTGACTACTTTATTTCTAAATAAGAAATTCCCTACCTGCTTCCTACAAGCAGTTCAGAATGCCATGCCTTGGTTGTCCTAGTGTGAATAATTTTCAGCTACTTTAAAATTATATTGTACTTTCTCAAGCATGTCATATCCTTTCCTATTAGAGTATCTATATTACTTGTTACTGATTTACCTGAAGGCAATCTGATTAATTTCTAGGTTTTTACCATATTCTTGTCATCTTGCCAATTACATTTTAAGTGTTAGACTAGACTAAGATGTACTAGTTGTATAGAATATAACTAGATTTATTATGGCAATGTTTATTTTGTCATTTTGCTTCATCTGTTTTGTTGTTGAAGTACTTTAAATTTCATACGTTCATGGCATTTCACTGTAAAGACTTTAATGTGTATTTCTTAAAATAAAACTTTTTTTCCTCCTTAA (SEQ ID NO: 196) >NP_000565.1 complement decay-accelerating factor isoform1 preproprotein [Homo sapiens]MTVARPSVPAALPLLGELPRLLLLVLLCLPAVWGDCGLPPDVPNAQPALEGRTSFPEDTVITYKCEESFVKIPGEKDSVICLKGSQWSDIEEFCNRSCEVPTRLNSASLKQPYITQNYFPVGTVVEYECRPGYRREPSLSPKLTCLQNLKWSTAVEFCKKKSCPNPGEIRNGQIDVPGGILFGATISFSCNTGYKLFGSTSSFCLISGSSVQWSDPLPECREIYCPAPPQIDNGIIQGERDHYGYRQSVTYACNKGFTMIGEHSIYCTVNNDEGEWSGPPPECRGKSLTSKVPPTVQKPTTVNVPTTEVSPTSQKTTTKTTTPNAQATRSTPVSRTTKHFHETTPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 197) Human CD59>NM_203330.2 Homo sapiens CD59 molecule (CD59 bloodGlycosylphosphatidylinositol group) (CD59), transcript variant 1, mRNA(GPI) GGGGCCGGGGGGCGGAGCCTTGCGGGCTGGAGCGAAAGAATGCGGGGGCTGAGCGCAGAAGCGGCTCGAGGCTGGAAGAGGATCTTGGGCGCCGCCAGTCTCTCTCTGTTGCCCAAGCTGGAGTGCAGTGGCACAGTCTTGGCTCACTGCAACCTCCACCTCCTGGGTGCAAGCGATTCTCGTGTCTCAGCCTCTCAAGTAGCTGGGATTACAGTCTTTAGCACCAGTTGGTGTAGGAGTTGAGACCTACTTCACAGTAGTTCTGTGGACAATCACAATGGGAATCCAAGGAGGGTCTGTCCTGTTCGGGCTGCTGCTCGTCCTGGCTGTCTTCTGCCATTCAGGTCATAGCCTGCAGTGCTACAACTGTCCTAACCCAACTGCTGACTGCAAAACAGCCGTCAATTGTTCATCTGATTTTGATGCGTGTCTCATTACCAAAGCTGGGTTACAAGTGTATAACAAGTGTTGGAAGTTTGAGCATTGCAATTTCAACGACGTCACAACCCGCTTGAGGGAAAATGAGCTAACGTACTACTGCTGCAAGAAGGACCTGTGTAACTTTAACGAACAGCTTGAAAATGGTGGGACATCCTTATCAGAGAAAACAGTTCTTCTGCTGGTGACTCCATTTCTGGCAGCAGCCTGGAGCCTTCATCCCTAAGTCAACACCAGGAGAGCTTCTCCCAAACTCCCCGTTCCTGCGTAGTCCGCTTTCTCTTGCTGCCACATTCTAAAGGCTTGATATTTTCCAAATGGATCCTGTTGGGAAAGAATAAAATTAGCTTGAGCAACCTGGCTAAGATAGAGGGGCTCTGGGAGACTTTGAAGACCAGTCCTGTTTGCAGGGAAGCCCCACTTGAAGGAAGAAGTCTAAGAGTGAAGTAGGTGTGACTTGAACTAGATTGCATGCTTCCTCCTTTGCTCTTGGGAAGACCAGCTTTGCAGTGACAGCTTGAGTGGGTTCTCTGCAGCCCTCAGATTATTTTTCCTCTGGCTCCTTGGATGTAGTCAGTTAGCATCATTAGTACATCTTTGGAGGGTGGGGCAGGAGTATATGAGCATCCTCTCTCACATGGAACGCTTTCATAAACTTCAGGGATCCCGTGTTGCCATGGAGGCATGCCAAATGTTCCATATGTGGGTGTCAGTCAGGGACAACAAGATCCTTAATGCAGAGCTAGAGGACTTCTGGCAGGGAAGTGGGGAAGTGTTCCAGATAGCAGGGCATGAAAACTTAGAGAGGTACAAGTGGCTGAAAATCGAGTTTTTCCTCTGTCTTTAAATTTTATATGGGCTTTGTTATCTTCCACTGGAAAAGTGTAATAGCATACATCAATGGTGTGTTAAAGCTATTTCCTTGCCTTTTTTTTATTGGAATGGTAGGATATCTTGGCTTTGCCACACACAGTTACAGAGTGAACACTCTACTACATGTGACTGGCAGTATTAAGTGTGCTTATTTTAAATGTTACTGGTAGAAAGGCAGTTCAGGTATGTGTGTATATAGTATGAATGCAGTGGGGACACCCTTTGTGGTTACAGTTTGAGACTTCCAAAGGTCATCCTTAATAACAACAGATCTGCAGGGGTATGTTTTACCATCTGCATCCAGCCTCCTGCTAACTCCTAGCTGACTCAGCATAGATTGTATAAAATACCTTTGTAACGGCTCTTAGCACACTCACAGATGTTTGAGGCTTTCAGAAGCTCTTCTAAAAAATGATACACACCTTTCACAAGGGCAAACTTTTTCCTTTTCCCTGTGTATTCTAGTGAATGAATCTCAAGATTCAGTAGACCTAATGACATTTGTATTTTATGATCTTGGCTGTATTTAATGGCATAGGCTGACTTTTGCAGATGGAGGAATTTCTTGATTAATGTTGAAAAAAAACCCTTGATTATACTCTGTTGGACAAACCGAGTGCAATGAATGATGCTTTTCTGAAAATGAAATATAACAAGTGGGTGAATGTGGTTATGGCCGAAAAGGATATGCAGTATGCTTAATGGTAGCAACTGAAAGAAGACATCCTGAGCAGTGCCAGCTTTCTTCTGTTGATGCCGTTCCCTGAACATAGGAAAATAGAAACTTGCTTATCAAAACTTAGCATTACCTTGGTGCTCTGTGTTCTCTGTTAGCTCAGTGTCTTTCCTTACATCAATAGGTTTTTTTTTTTTTTTTTGGCCTGAGGAAGTACTGACCATGCCCACAGCCACCGGCTGAGCAAAGAAGCTCATTTCATGTGAGTTCTAAGGAATGAGAAACAATTTTGATGAATTTAAGCAGAAAATGAATTTCTGGGAACTTTTTTGGGGGCGGGGGGGTGGGGAATTCAGCCACACTCCAGAAAGCCAGGAGTCGACAGTTTTGGAAGCCTCTCTCAGGATTGAGATTCTAGGATGAGATTGGCTTACTGCTATCTTGTGTCATGTACCCACTTTTTGGCCAGACTACACTGGGAAGAAGGTAGTCCTCTAAAGCAAAATCTGAGTGCCACTAAATGGGGAGATGGGGCTGTTAAGCTGTCCAAATCAACAAGGGTCATATAAATGGCCTTAAACTTTGGGGTTGCTTTCTGCAAAAAGTTGCTGTGACTCATGCCATAGACAAGGTTGAGTGCCTGGACCCAAAGGCAATACTGTAATGTAAAGACATTTATAGTACTAGGCAAACAGCACCCCAGGTACTCCAGGCCCTCCTGGCTGGAGAGGGCTGTGGCAATAGAAAATTAGTGCCAACTGCAGTGAGTCAGCCTAGGTTAAATAGAGAGTGTAAGAGTGCTGGACAGGAACCTCCACCCTCATGTCACATTTCTTCAATGTGACCCTTCTGGCCCCTCTCCTCCTGACAGCGGAACAATGACTGCCCCGATAGGTGAGGCTGGAGGAAGAATCAGTCCTGTCCTTGGCAAGCTCTTCACTATGACAGTAAAGGCTCTCTGCCTGCTGCCAAGGCCTGTGACTTTCTAACCTGGCCTCACGCTGGGTAAGCTTAAGGTAGAGGTGCAGGATTAGCAAGCCCACCTGGCTACCAGGCCGACAGCTACATCCTCCAACTGACCCTGATCAACGAAGAGGGATTCATGTGTCTGTCTCAGTTGGTTCCAAATGAAACCAGGGAGCAGGGGAGTTAGGAATCGAACACCAGTCATGCCTACTGGCTCTCTGCTCGAGAGCCAATACCCTGTGCCCTCCACTCATCTGGATTTACAGGAACTGTCATAGTGTTCAGTATTGGGTGGTGATAAGCCCATTGGATTGTCCCCTTGGGGGGATGAGCTAGGGGTGCAAGGAACACCTGATGAGTAGATAAGTGGAGCTCATGGTATTTCCTGAAAGATGCTAATCTATTTGCCAAACTTGGTCTTGAATGTACTGGGGGCTTCAAGGTATGGGTATATTTTTCTTGTGTCCTTGCAGTTAGCCCCCATGTCTTATGTGTGTCCTGAAAAAATAAGAGCCTGCCCAAGACTTTGGGCCTCTTGACAGAATTAACCACTTTTATACATCTGAGTTCTCTTGGTAAGTTCTTTAGCAGTGTTCAAAGTCTACTAGCTCGCATTAGTTTCTGTTGCTGCCAACAGATCTGAACTAATGCTAACAGATCCCCCTGAGGGATTCTTGATGGGCTGAGCAGCTGGCTGGAGCTAGTACTGACTGACATTCATTGTGATGAGGGCAGCTTTCTGGTACAGGATTCTAAGCTCTATGTTTTATATACATTTTCATCTGTACTTGCACCTCACTTTACACAAGAGGAAACTATGCAAAGTTAGCTGGATCGCTCAAGGTCACTTAGGTAAGTTGGCAAGTCCATGCTTCCCACTCAGCTCCTCAGGTCAGCAAGTCTACTTCTCTGCCTATTTTGTATACTCTCTTTAATATGTGCCTAGCTTTGGAAAGTCTAGAATGGGTCCCTGGTGCCTTTTTACTTTGAAGAAATCAGTTTCTGCCTCTTTTTGGAAAAGAAAACAAAGTGCAATTGTTTTTTACTGGAAAGTTACCCAATAGCATGAGGTGAACAGGACGTAGTTAGGCCTTCCTGTAAACAGAAAATCATATCAAAACACTATCTTCCCATCTGTTTCTCAATGCCTGCTACTTCTTGTAGATATTTCATTTCAGGAGAGCAGCAGTTAAACCCGTGGATTTTGTAGTTAGGAACCTGGGTTCAAACCCTCTTCCACTAATTGGCTATGTCTCTGGACAAGTTTTTTTTTTTTTTTTTTTTTAAACCCTTTCTGAACTTTCACTTTCTATGTCTACCTCAAAGAATTGTTGTGAGGCTTGAGATAATGCATTTGTAAAGGGTCTGCCAGATAGGAAGATGCTAGTTATGGATTTACAAGGTTGTTAAGGCTGTAAGAGTCTAAAACCTACAGTGAATCACAATGCATTTACCCCCACTGACTTGGACATAAGTGAAAACTAGCCAGAAGTCTCTTTTTCAAATTACTTACAGGTTATTCAATATAAAATTTTTGTAATGGATAATCTTATTTATCTAAACTAAAGCTTCCTGTTTATACACACTCCTGTTATTCTGGGATAAGATAAATGACCACAGTACCTTAATTTCTAGGTGGGTGCCTGTGATGGTTCATTGTAGGTAAGGACATTTTCTCTTTTTCAGCAGCTGTGTAGGTCCAGAGCCTCTGGGAGAGGAGGGGGGTAGCATGCACCCAGCAGGGGACTGAACTGGGAAACTCAAGGTTCTTTTTACTGTGGGGTAGTGAGCTGCCTTTCTGTGATCGGTTTCCCTAGGGATGTTGCTGTTCCCCTCCTTGCTATTCGCAGCTACATACAACGTGGCCAACCCCAGTAGGCTGATCCTATATATGATCAGTGCTGGTGCTGACTCTCAATAGCCCCACCCAAGCTGGCTATAGGTTTACAGATACATTAATTAGGCAACCTAAAATATTGATGCTGGTGTTGGTGTGACATAATGCTATGGCCAGAACTGAAACTTAGAGTTATAATTCATGTATTAGGGTTCTCCAGAGGGACAGAATTAGTAGGATATATGTATATATGAAAGGGAGGTTATTAGGGAGAACTGGCTCCCACAGTTAGAAGGCGAAGTCGCACAATAGGCCGTCTGCAAGCTGGGTTAGAGAGAAGCCAGTAGTGGCTCAGCCTGAGTTCAAAAACCTCAAAACTGGGGAAGCTGACAGTGCAGCCAGCCTTCAGTCTGTGGCCAAAGGCCCAAGAGCCCCTGGCAACCAACCCACTGGTGCAAGTCCTAGATTCCAAAGGCTGAAGAACCTGGAGTCTGATGTCCAAGAGCAGGAAGAGTGGAAGAAAGCCAGAAGACTCAGCAAACAAGGTAGACAGTGTCTACCACCATAGTGGCCATACCAAAGAGGCTACCGATTCCTTCCTGCTACCTGGATCCCTGAAGTTGCCCTGGTCTCTGCACCTTCTAAACCTAGTTCTTAAGAGCTTTCCATTACATGAGCTGTCTCAAAGCCCTCCAATAAATTCTCAGTGTAAGCTTCTGTTGCTTGTGGACAGAAAATTCTGACAGACCTACCCTATAAGTGTTACTGTCAGGATAACATGAGAACGCACAACAGTAAGTGGTCACTAAGTGTTAGCTACGGTTATTTTGCCCAAGGTAGCATGGCTAGTTGATGCCGGTTGATGGGGCTTAAACCCAGCTCCCTCATCTTCCAGGCCTCTGTACTCCCTATTCCACTAAACTACCTCTCAGGTTTATTTTTTTAAATTCTTACTCTGCAAGTACATAGGACCACATTTACCTGGGAAAACAAGAATAAAGGCTGCTCTGCATTTTTTAGAAACTTTTTTGAAAGGGAGATGGGAATGCCTGCACCCCCAAGTCCAGACCAACACAATGGTTAATTGAGATGAATAATAAAGGAAAGACTGTTCTGGGCTTCCCAGAATAGCTTGGTCCTTAAATTGTGGCACAAACAACCTCCTGTCAGAGCCAGCCTCCTGCCAGGAAGAGGGGTAGGAGACTAGAGGCCGTGTGTGCAGCCTTGCCCTGAAGGCTAGGGTGACAATTTGGAGGCTGTCCAAACACCCTGGCCTCTAGAGCTGGCCTGTCTATTTGAAATGCCGGCTCTGATGCTAATCGGCGACCCTCAGGCAAGTTACTTAACCTTACATGCCTCAGTTTTCTCATCTGGAAAATGAGAACCCTAGGTTTAGGGTTGTTAGAAAAGTTAAATGAGTTAAGACAAGTGCCTGGGACACAGTAGCCTCTTGTGTGTGTTTATCATTATGTCCTCAGCAGGTCGTAGAAGCAGCTTCTCAGGTGTGAGGCTGGCGCGATTATCTGGAGTGGGTTGGGTTTTCTAGGATGGACCCCCTGCTGCATTTTCCTCATTCATCCACCAGGGCTTAATGGGGAATCAAGGAATCCATGTGTAACTGTATAATAACTGTAGCCACACTCCAATGACCACCTACTAGTTGTCCCTGGCACTGCTTATACATATGTCCATCAAATCAATCCTATGAAGTAGATACTGTCTTCATTTTATAGATCAGAGACAATTGGGGTTCAGAGAGCTGATGTGATTTTCCCAGGGTCACAGAGAGTCCCAGATTCAGGCACAACTCTTGTATTCCAAGACACAACCACTACATGTCCAAAGGCTGCCCAGAGCCACCGGGCACGGCAAATTGTGACATATCCCTAAAGAGGCTGAGCACCTGGTCAGGATCTGATGGCTGACAGTGTGTCCAGATGCAGAGCTGGAGTGGGGGAGGGGAAGGGGGGCTCCTTGGGACAGAGAAGGCTTTCTGTGCTTTCTCTGAAGGGAGCAGTCTGAGGACCAAGGGAACCCGGCAAACAGCACCTCAGGTACTCCAGGCCCTCCTGGCTGGAGAGGGCTGTGGCAATGGAAAATTAGTGCCAACTGCAATGAGTCAGCCTCGGTTAAATAGAGAGTGAAGAATGCTGGACAGGAACCTCCACCCTCATGTCACATTTCTTCAGTGTGACCCTTCTGGCCCCTCTCCTCCTGACAGCGGAACAATGACTGCCCCGATAGGTGAGGCTGGAGGAAGAATCAGTCCTGTCCTTGGCAAGCTCTTCACTATGACAGTAAAGGCTCTCTGCCTGCTGCCAAGGCCTGTGACTTTCTAACCTGGCCTCACGCTGGGTAAGCTTAAGGTAGAGGTGCAGGATTAGCAAGCCCACCTGGCTACCAGGCCGACAGCTACATCTTTCAACTGACCCTGATCAACGAAGAGGGACTTGTGTCTCTCAGTTGGTTCCAAATGAAACCAGGGAGCAGGGGCGTTAGGAAGCTCCAACAGGATGGTACTTAATGGGGCATTTGAGTGGAGAGGTAGGTGACATAGTGCTTTGGAGCCCAGGGAGGGAAAGGTTCTGCTGAAGTTGAATTCAAGACTGTTCTTTCATCACAAACTTGAGTTTCCTGGACATTTGTTTGCAGAAACAACCGTAGGGTTTTGCCTTAACCTCGTGGGTTTATTATTACCTCATAGGGACTTTGCCTCCTGACAGCAGTTTATGGGTGTTCATTGTGGCACTTGAGTTTTCTTGCATACTTGTTAGAGAAACCAAGTTTGTCATCAACTTCTTATTTAACCCCCTGGCTATAACTTCATGGATTATGTTATAATTAAGCCATCCAGAGTAAAATCTGTTTAGATTATCTTGGAGTAAGGGGGAAAAAATCTGTAATTTTTTCTCCTCAACTAGATATATACATAAAAAATGATTGTATTGCTTCATTTAAAAAATATAACGCAAAATCTCTTTTCCTTCTAAAAAAAAAAAAAAAAAA (SEQ ID NO: 197)>NP_976075.1 CD59 glycoprotein preproprotein [Homo sapiens]MGIQGGSVLFGLLLVLAVFCHSGHSLQCYNCPNPTADCKTAVNCSSDFDACLITKAGLQVYNKCWKFEHCNFNDVTTRLRENELTYYCCKKDLCNFNEQLENGGTSLSEKTVLLLVTPFLAAAWSLHP (SEQ ID NO: 198) Human C1C2 fromNM_005928.4 Homo sapiens milk fat globule-EGF factor 8 MFGE8protein (MFGE8), transcript variant 1, mRNAAGAACCCCGCGGGGTCTGAGCAGCCCAGCGTGCCCATTCCAGCGCCCGCGTCCCCGCAGCATGCCGCGCCCCCGCCTGCTGGCCGCGCTGTGCGGCGCGCTGCTCTGCGCCCCCAGCCTCCTCGTCGCCCTGGATATCTGTTCCAAAAACCCCTGCCACAACGGTGGTTTATGCGAGGAGATTTCCCAAGAAGTGCGAGGAGATGTCTTCCCCTCGTACACCTGCACGTGCCTTAAGGGCTACGCGGGCAACCACTGTGAGACGAAATGTGTCGAGCCACTGGGCCTGGAGAATGGGAACATTGCCAACTCACAGATCGCCGCCTCGTCTGTGCGTGTGACCTTCTTGGGTTTGCAGCATTGGGTCCCGGAGCTGGCCCGCCTGAACCGCGCAGGCATGGTCAATGCCTGGACACCCAGCAGCAATGACGATAACCCCTGGATCCAGGTGAACCTGCTGCGGAGGATGTGGGTAACAGGTGTGGTGACGCAGGGTGCCAGCCGCTTGGCCAGTCATGAGTACCTGAAGGCCTTCAAGGTGGCCTACAGCCTTAATGGACACGAATTCGATTTCATCCATGATGTTAATAAAAAACACAAGGAGTTTGTGGGTAACTGGAACAAAAACGCGGTGCATGTCAACCTGTTTGAGACCCCTGTGGAGGCTCAGTACGTGAGATTGTACCCCACGAGCTGCCACACGGCCTGCACTCTGCGCTTTGAGCTACTGGGCTGTGAGCTGAACGGATGCGCCAATCCCCTGGGCCTGAAGAATAACAGCATCCCTGACAAGCAGATCACGGCCTCCAGCAGCTACAAGACCTGGGGCTTGCATCTCTTCAGCTGGAACCCCTCCTATGCACGGCTGGACAAGCAGGGCAACTTCAACGCCTGGGTTGCGGGGAGCTACGGTAACGATCAGTGGCTGCAGGTGGACCTGGGCTCCTCGAAGGAGGTGACAGGCATCATCACCCAGGGGGCCCGTAACTTTGGCTCTGTCCAGTTTGTGGCATCCTACAAGGTTGCCTACAGTAATGACAGTGCGAACTGGACTGAGTACCAGGACCCCAGGACTGGCAGCAGTAAGATCTTCCCTGGCAACTGGGACAACCACTCCCACAAGAAGAACTTGTTTGAGACGCCCATCCTGGCTCGCTATGTGCGCATCCTGCCTGTAGCCTGGCACAACCGCATCGCCCTGCGCCTGGAGCTGCTGGGCTGTTAGTGGCCACCTGCCACCCCCAGGTCTTCCTGCTTTCCATGGGCCCGCTGCCTCTTGGCTTCTCAGCCCCTTTAAATCACCATAGGGCTGGGGACTGGGGAAGGGGAGGGTGTTCAGAGGCAGCACCACCACACAGTCACCCCTCCCTCCCTCTTTCCCACCCTCCACCTCTCACGGGCCCTGCCCCAGCCCCTAAGCCCCGTCCCCTAACCCCCAGTCCTCACTGTCCTGTTTTCTTAGGCACTGAGGGATCTGAGTAGGTCTGGGATGGACAGGAAAGGGCAAAGTAGGGCGTGTGGTTTCCCTGCCCCTGTCCGGACCGCCGATCCCAGGTGCGTGTGTCTCTGTCTCTCCTAGCCCCTCTCTCACACATCACATTCCCATGGTGGCCTCAAGAAAGGCCCGGAAGCGCCAGGCTGGAGATAACAGCCTCTTGCCCGTCGGCCCTGCGTCGGCCCTGGGGTACCATGTGGCCACAACTGCTGTGGCCCCCTGTCCCCAAGACACTTCCCCTTGTCTCCCTGGTTGCCTCTCTTGCCCCTTGTCCTGAAGCCCAGCGACACAGAAGGGGGTGGGGCGGGTCTATGGGGAGAAAGGGAGCGAGGTCAGAGGAGGGCATGGGTTGGCAGGGTGGGCGTTTGGGGCCCTCTATGCTGGCTTTTCACCCCAGAGGACACAGGCAGCTTCCAAAATATATTTATCTTCTTCACGGGAA (SEQ ID NO: 199)>NP_005919.2 lactadherin isoform a preproprotein [Homo sapiens]MPRPRLLAALCGALLCAPSLLVALDICSKNPCHNGGLCEEISQEVRGDVFPSYTCTCLKGYAGNHCETKCVEPLGLENGNIANSQIAASSVRVTFLGLQHWVPELARLNRAGMVNAWTPSSNDDNPWIQVNLLRRMWVTGVVTQGASRLASHEYLKAFKVAYSLNGHEFDFIHDVNKKHKEFVGNWNKNAVHVNLFETPVEAQYVRLYPTSCHTACTLRFELLGCELNGCANPLGLKNNSIPDKQITASSSYKTWGLHLFSWNPSYARLDKQGNFNAWVAGSYGNDQWLQVDLGSSKEVTGIITQGARNFGSVQFVASYKVAYSNDSANWTEYQDPRTGSSKIFPGNWDNHSHKKNLFETPILARYVRILPVAWHNRIALRLELLGC (SEQ ID NO: 200)Human 4F2 (CD98) >NM_002394.6 Homo sapiens solute carrier family 3member 2 (SLC3A2), transcript variant 3, mRNAGCATTGCGGCTTGGTTTTCTCACCCAGTGCATGTGGCAGGAGCGGTGAGATCACTGCCTCACGGCGATCCTGGACTGACGGTCACGACTGCCTACCCTCTAACCCTGTTCTGAGCTGCCCCTTGCCCACACACCCCAAACCTGTGTGCAGGATCCGCCTCCATGGAGCTACAGCCTCCTGAAGCCTCGATCGCCGTCGTGTCGATTCCGCGCCAGTTGCCTGGCTCACATTCGGAGGCTGGTGTCCAGGGTCTCAGCGCGGGGGACGACTCAGAGTTGGGGTCTCACTGTGTTGCCCAGACTGGTCTCGAACTCTTGGCCTCAGGTGATCCTCTTCCCTCAGCTTCCCAGAATGCCGAGATGATAGAGACGGGGTCTGACTGTGTTACCCAGGCTGGTCTTCAACTCTTGGCCTCAAGTGATCCTCCTGCCTTAGCTTCCAAGAATGCTGAGGTTACAGGCACCATGAGCCAGGACACCGAGGTGGATATGAAGGAGGTGGAGCTGAATGAGTTAGAGCCCGAGAAGCAGCCGATGAACGCGGCGTCTGGGGCGGCCATGTCCCTGGCGGGAGCCGAGAAGAATGGTCTGGTGAAGATCAAGGTGGCGGAAGACGAGGCGGAGGCGGCAGCCGCGGCTAAGTTCACGGGCCTGTCCAAGGAGGAGCTGCTGAAGGTGGCAGGCAGCCCCGGCTGGGTACGCACCCGCTGGGCACTGCTGCTGCTCTTCTGGCTCGGCTGGCTCGGCATGCTTGCTGGTGCCGTGGTCATAATCGTGCGAGCGCCGCGTTGTCGCGAGCTACCGGCGCAGAAGTGGTGGCACACGGGCGCCCTCTACCGCATCGGCGACCTTCAGGCCTTCCAGGGCCACGGCGCGGGCAACCTGGCGGGTCTGAAGGGGCGTCTCGATTACCTGAGCTCTCTGAAGGTGAAGGGCCTTGTGCTGGGTCCAATTCACAAGAACCAGAAGGATGATGTCGCTCAGACTGACTTGCTGCAGATCGACCCCAATTTTGGCTCCAAGGAAGATTTTGACAGTCTCTTGCAATCGGCTAAAAAAAAGAGCATCCGTGTCATTCTGGACCTTACTCCCAACTACCGGGGTGAGAACTCGTGGTTCTCCACTCAGGTTGACACTGTGGCCACCAAGGTGAAGGATGCTCTGGAGTTTTGGCTGCAAGCTGGCGTGGATGGGTTCCAGGTTCGGGACATAGAGAATCTGAAGGATGCATCCTCATTCTTGGCTGAGTGGCAAAATATCACCAAGGGCTTCAGTGAAGACAGGCTCTTGATTGCGGGGACTAACTCCTCCGACCTTCAGCAGATCCTGAGCCTACTCGAATCCAACAAAGACTTGCTGTTGACTAGCTCATACCTGTCTGATTCTGGTTCTACTGGGGAGCATACAAAATCCCTAGTCACACAGTATTTGAATGCCACTGGCAATCGCTGGTGCAGCTGGAGTTTGTCTCAGGCAAGGCTCCTGACTTCCTTCTTGCCGGCTCAACTTCTCCGACTCTACCAGCTGATGCTCTTCACCCTGCCAGGGACCCCTGTTTTCAGCTACGGGGATGAGATTGGCCTGGATGCAGCTGCCCTTCCTGGACAGCCTATGGAGGCTCCAGTCATGCTGTGGGATGAGTCCAGCTTCCCTGACATCCCAGGGGCTGTAAGTGCCAACATGACTGTGAAGGGCCAGAGTGAAGACCCTGGCTCCCTCCTTTCCTTGTTCCGGCGGCTGAGTGACCAGCGGAGTAAGGAGCGCTCCCTACTGCATGGGGACTTCCACGCGTTCTCCGCTGGGCCTGGACTCTTCTCCTATATCCGCCACTGGGACCAGAATGAGCGTTTTCTGGTAGTGCTTAACTTTGGGGATGTGGGCCTCTCGGCTGGACTGCAGGCCTCCGACCTGCCTGCCAGCGCCAGCCTGCCAGCCAAGGCTGACCTCCTGCTCAGCACCCAGCCAGGCCGTGAGGAGGGCTCCCCTCTTGAGCTGGAACGCCTGAAACTGGAGCCTCACGAAGGGCTGCTGCTCCGCTTCCCCTACGCGGCCTGACTTCAGCCTGACATGGACCCACTACCCTTCTCCTTTCCTTCCCAGGCCCTTTGGCTTCTGATTTTTCTCTTTTTTAAAAACAAACAAACAAACTGTTGCAGATTATGAGTGAACCCCCAAATAGGGTGTTTTCTGCCTTCAAATAAAAGTCACCCCTGCATGGTGAA (SEQ ID NO:201) >NP_002385.3 4F2 cell-surface antigen heavy chainisoform c [Homo sapiens]MELQPPEASIAVVSIPRQLPGSHSEAGVQGLSAGDDSELGSHCVAQTGLELLASGDPLPSASQNAEMIETGSDCVTQAGLQLLASSDPPALASKNAEVTGTMSQDTEVDMKEVELNELEPEKQPMNAASGAAMSLAGAEKNGLVKIKVAEDEAEAAAAAKFTGLSKEELLKVAGSPGWVRTRWALLLLFWLGWLGMLAGAVVIIVRAPRCRELPAQKWWHTGALYRIGDLQAFQGHGAGNLAGLKGRLDYLSSLKVKGLVLGPIHKNQKDDVAQTDLLQIDPNFGSKEDFDSLLQSAKKKSIRVILDLTPNYRGENSWFSTQVDTVATKVKDALEFWLQAGVDGFQVRDIENLKDASSFLAEWQNITKGFSEDRLLIAGTNSSDLQQILSLLESNKDLLLTSSYLSDSGSTGEHTKSLVTQYLNATGNRWCSWSLSQARLLTSFLPAQLLRLYQLMLFTLPGTPVFSYGDEIGLDAAALPGQPMEAPVMLWDESSFPDIPGAVSANMTVKGQSEDPGSLLSLFRRLSDQRSKERSLLHGDFHAFSAGPGLFSYIRHWDQNERFLVVLNFGDVGLSAGLQASDLPASASLPAKADLLLSTQPGREEGSPLELERLKLEPHEGLLLRFPYAA (SEQ ID NO: 202) Human TFR2>NM_003227.4 Homo sapiens transferrin receptor 2(TFR2), transcript variant 1, mRNAATCGCTGGGGGACAGCCTGCAGGCTTCAGGAGGGGACACAAGCATGGAGCGGCTTTGGGGTCTATTCCAGAGAGCGCAACAACTGTCCCCAAGATCCTCTCAGACCGTCTACCAGCGTGTGGAAGGCCCCCGGAAAGGGCACCTGGAGGAGGAAGAGGAAGACGGGGAGGAGGGGGCGGAGACATTGGCCCACTTCTGCCCCATGGAGCTGAGGGGCCCTGAGCCCCTGGGCTCTAGACCCAGGCAGCCAAACCTCATTCCCTGGGCGGCAGCAGGACGGAGGGCTGCCCCCTACCTGGTCCTGACGGCCCTGCTGATCTTCACTGGGGCCTTCCTACTGGGCTACGTCGCCTTCCGAGGGTCCTGCCAGGCGTGCGGAGACTCTGTGTTGGTGGTCAGTGAGGATGTCAACTATGAGCCTGACCTGGATTTCCACCAGGGCAGACTCTACTGGAGCGACCTCCAGGCCATGTTCCTGCAGTTCCTGGGGGAGGGGCGCCTGGAGGACACCATCAGGCAAACCAGCCTTCGGGAACGGGTGGCAGGCTCGGCCGGGATGGCCGCTCTGACTCAGGACATTCGCGCGGCGCTCTCCCGCCAGAAGCTGGACCACGTGTGGACCGACACGCACTACGTGGGGCTGCAATTCCCGGATCCGGCTCACCCCAACACCCTGCACTGGGTCGATGAGGCCGGGAAGGTCGGAGAGCAGCTGCCGCTGGAGGACCCTGACGTCTACTGCCCCTACAGCGCCATCGGCAACGTCACGGGAGAGCTGGTGTACGCCCACTACGGGCGGCCCGAAGACCTGCAGGACCTGCGGGCCAGGGGCGTGGATCCAGTGGGCCGCCTGCTGCTGGTGCGCGTGGGGGTGATCAGCTTCGCCCAGAAGGTGACCAATGCTCAGGACTTCGGGGCTCAAGGAGTGCTCATATACCCAGAGCCAGCGGACTTCTCCCAGGACCCACCCAAGCCAAGCCTGTCCAGCCAGCAGGCAGTGTATGGACATGTGCACCTGGGAACTGGAGACCCCTACACACCTGGCTTCCCTTCCTTCAATCAAACCCAGTTCCCTCCAGTTGCATCATCAGGCCTTCCCAGCATCCCAGCCCAGCCCATCAGTGCAGACATTGCCTCCCGCCTGCTGAGGAAGCTCAAAGGCCCTGTGGCCCCCCAAGAATGGCAGGGGAGCCTCCTAGGCTCCCCTTATCACCTGGGCCCCGGGCCACGACTGCGGCTAGTGGTCAACAATCACAGGACCTCCACCCCCATCAACAACATCTTCGGCTGCATCGAAGGCCGCTCAGAGCCAGATCACTACGTTGTCATCGGGGCCCAGAGGGATGCATGGGGCCCAGGAGCAGCTAAATCCGCTGTGGGGACGGCTATACTCCTGGAGCTGGTGCGGACCTTTTCCTCCATGGTGAGCAACGGCTTCCGGCCCCGCAGAAGTCTCCTCTTCATCAGCTGGGACGGTGGTGACTTTGGAAGCGTGGGCTCCACGGAGTGGCTAGAGGGCTACCTCAGCGTGCTGCACCTCAAAGCCGTAGTGTACGTGAGCCTGGACAACGCAGTGCTGGGGGATGACAAGTTTCATGCCAAGACCAGCCCCCTTCTGACAAGTCTCATTGAGAGTGTCCTGAAGCAGGTGGATTCTCCCAACCACAGTGGGCAGACTCTCTATGAACAGGTGGTGTTCACCAATCCCAGCTGGGATGCTGAGGTGATCCGGCCCCTACCCATGGACAGCAGTGCCTATTCCTTCACGGCCTTTGTGGGAGTCCCTGCCGTCGAGTTCTCCTTTATGGAGGACGACCAGGCCTACCCATTCCTGCACACAAAGGAGGACACTTATGAGAACCTGCATAAGGTGCTGCAAGGCCGCCTGCCCGCCGTGGCCCAGGCCGTGGCCCAGCTCGCAGGGCAGCTCCTCATCCGGCTCAGCCACGATCGCCTGCTGCCCCTCGACTTCGGCCGCTACGGGGACGTCGTCCTCAGGCACATCGGGAACCTCAACGAGTTCTCTGGGGACCTCAAGGCCCGCGGGCTGACCCTGCAGTGGGTGTACTCGGCGCGGGGGGACTACATCCGGGCGGCGGAAAAGCTGCGGCAGGAGATCTACAGCTCGGAGGAGAGAGACGAGCGACTGACACGCATGTACAACGTGCGCATAATGCGGGTGGAGTTCTACTTCCTTTCCCAGTACGTGTCGCCAGCCGACTCCCCGTTCCGCCACATCTTCATGGGCCGTGGAGACCACACGCTGGGCGCCCTGCTGGACCACCTGCGGCTGCTGCGCTCCAACAGCTCCGGGACCCCCGGGGCCACCTCCTCCACTGGCTTCCAGGAGAGCCGTTTCCGGCGTCAGCTAGCCCTGCTCACCTGGACGCTGCAAGGGGCAGCCAATGCGCTTAGCGGGGATGTCTGGAACATTGATAACAACTTCTGAGGCCCTGGGGATCCTCACATCCCCGTCCCCCAGTCAAGAGCTCCTCTGCTCCTCGCTTGAATGATTCAGGGTCAGGGAGGTGGCTCAGAGTCCACCTCTCATTGCTGATCAATTTCTCATTACCCCTACACATCTCTCCACGGAGCCCAGACCCCAGCACAGATATCCACACACCCCAGCCCTGCAGTGTAGCTGACCCTAATGTGACGGTCATACTGTCGGTTAATCAGAGAGTAGCATCCCTTCAATCACAGCCCCTTCCCCTTTCTGGGGTCCTCCATACCTAGAGACCACTCTGGGAGGTTTGCTAGGCCCTGGGACCTGGCCAGCTCTGTTAGTGGGAGAGATCGCTGGCACCATAGCCTTATGGCCAACAGGTGGTCTGTGGTGAAAGGGGCGTGGAGTTTCAATATCAATAAACCACCTGATATCAATAA (SEQ ID NO: 203) >NP_003218.2 transferrin receptor protein 2 isoform1 [Homo sapiens] MERLWGLFQRAQQLSPRSSQTVYQRVEGPRKGHLEEEEEDGEEGAETLAHFCPMELRGPEPLGSRPRQPNLIPWAAAGRRAAPYLVLTALLIFTGAFLLGYVAFRGSCQACGDSVLVVSEDVNYEPDLDFHQGRLYWSDLQAMFLQFLGEGRLEDTIRQTSLRERVAGSAGMAALTQDIRAALSRQKLDHVWTDTHYVGLQFPDPAHPNTLHWVDEAGKVGEQLPLEDPDVYCPYSAIGNVTGELVYAHYGRPEDLQDLRARGVDPVGRLLLVRVGVISFAQKVTNAQDFGAQGVLIYPEPADFSQDPPKPSLSSQQAVYGHVHLGTGDPYTPGFPSFNQTQFPPVASSGLPSIPAQPISADIASRLLRKLKGPVAPQEWQGSLLGSPYHLGPGPRLRLVVNNHRTSTPINNIFGCIEGRSEPDHYVVIGAQRDAWGPGAAKSAVGTAILLELVRTFSSMVSNGFRPRRSLLFISWDGGDFGSVGSTEWLEGYLSVLHLKAVVYVSLDNAVLGDDKFHAKTSPLLTSLIESVLKQVDSPNHSGQTLYEQVVFTNPSWDAEVIRPLPMDSSAYSFTAFVGVPAVEFSFMEDDQAYPFLHTKEDTYENLHKVLQGRLPAVAQAVAQLAGQLLIRLSHDRLLPLDFGRYGDVVLRHIGNLNEFSGDLKARGLTLQWVYSARGDYIRAAEKLRQEIYSSEERDERLTRMYNVRIMRVEFYFLSQYVSPADSPFRHIFMGRGDHTLGALLDHLRLLRSNSSGTPGATSSTGFQESRFRRQLALLTWTLQGAANALSGDVWNIDNNF (SEQ ID NO: 204) Human ADAM10>NM_001110.4 Homo sapiens ADAM metallopeptidasedomain 10 (ADAM10), transcript variant 1, mRNAGTTGCCGGCCCCTGAAGTGGAGCGAGAGGGAGGTGCTTCGCCGTTTCTCCTGCCAGGGGAGGTCCCGGCTTCCCGTGGAGGCTCCGGACCAAGCCCCTTCAGCTTCTCCCTCCGGATCGATGTGCTGCTGTTAACCCGTGAGGAGGCGGCGGCGGCGGCAGCGGCAGCGGAAGATGGTGTTGCTGAGAGTGTTAATTCTGCTCCTCTCCTGGGCGGCGGGGATGGGAGGTCAGTATGGGAATCCTTTAAATAAATATATCAGACATTATGAAGGATTATCTTACAATGTGGATTCATTACACCAAAAACACCAGCGTGCCAAAAGAGCAGTCTCACATGAAGACCAATTTTTACGTCTAGATTTCCATGCCCATGGAAGACATTTCAACCTACGAATGAAGAGGGACACTTCCCTTTTCAGTGATGAATTTAAAGTAGAAACATCAAATAAAGTACTTGATTATGATACCTCTCATATTTACACTGGACATATTTATGGTGAAGAAGGAAGTTTTAGCCATGGGTCTGTTATTGATGGAAGATTTGAAGGATTCATCCAGACTCGTGGTGGCACATTTTATGTTGAGCCAGCAGAGAGATATATTAAAGACCGAACTCTGCCATTTCACTCTGTCATTTATCATGAAGATGATATTAACTATCCCCATAAATACGGTCCTCAGGGGGGCTGTGCAGATCATTCAGTATTTGAAAGAATGAGGAAATACCAGATGACTGGTGTAGAGGAAGTAACACAGATACCTCAAGAAGAACATGCTGCTAATGGTCCAGAACTTCTGAGGAAAAAACGTACAACTTCAGCTGAAAAAAATACTTGTCAGCTTTATATTCAGACTGATCATTTGTTCTTTAAATATTACGGAACACGAGAAGCTGTGATTGCCCAGATATCCAGTCATGTTAAAGCGATTGATACAATTTACCAGACCACAGACTTCTCCGGAATCCGTAACATCAGTTTCATGGTGAAACGCATAAGAATCAATACAACTGCTGATGAGAAGGACCCTACAAATCCTTTCCGTTTCCCAAATATTGGTGTGGAGAAGTTTCTGGAATTGAATTCTGAGCAGAATCATGATGACTACTGTTTGGCCTATGTCTTCACAGACCGAGATTTTGATGATGGCGTACTTGGTCTGGCTTGGGTTGGAGCACCTTCAGGAAGCTCTGGAGGAATATGTGAAAAAAGTAAACTCTATTCAGATGGTAAGAAGAAGTCCTTAAACACTGGAATTATTACTGTTCAGAACTATGGGTCTCATGTACCTCCCAAAGTCTCTCACATTACTTTTGCTCACGAAGTTGGACATAACTTTGGATCCCCACATGATTCTGGAACAGAGTGCACACCAGGAGAATCTAAGAATTTGGGTCAAAAAGAAAATGGCAATTACATCATGTATGCAAGAGCAACATCTGGGGACAAACTTAACAACAATAAATTCTCACTCTGTAGTATTAGAAATATAAGCCAAGTTCTTGAGAAGAAGAGAAACAACTGTTTTGTTGAATCTGGCCAACCTATTTGTGGAAATGGAATGGTAGAACAAGGTGAAGAATGTGATTGTGGCTATAGTGACCAGTGTAAAGATGAATGCTGCTTCGATGCAAATCAACCAGAGGGAAGAAAATGCAAACTGAAACCTGGGAAACAGTGCAGTCCAAGTCAAGGTCCTTGTTGTACAGCACAGTGTGCATTCAAGTCAAAGTCTGAGAAGTGTCGGGATGATTCAGACTGTGCAAGGGAAGGAATATGTAATGGCTTCACAGCTCTCTGCCCAGCATCTGACCCTAAACCAAACTTCACAGACTGTAATAGGCATACACAAGTGTGCATTAATGGGCAATGTGCAGGTTCTATCTGTGAGAAATATGGCTTAGAGGAGTGTACGTGTGCCAGTTCTGATGGCAAAGATGATAAAGAATTATGCCATGTATGCTGTATGAAGAAAATGGACCCATCAACTTGTGCCAGTACAGGGTCTGTGCAGTGGAGTAGGCACTTCAGTGGTCGAACCATCACCCTGCAACCTGGATCCCCTTGCAACGATTTTAGAGGTTACTGTGATGTTTTCATGCGGTGCAGATTAGTAGATGCTGATGGTCCTCTAGCTAGGCTTAAAAAAGCAATTTTTAGTCCAGAGCTCTATGAAAACATTGCTGAATGGATTGTGGCTCATTGGTGGGCAGTATTACTTATGGGAATTGCTCTGATCATGCTAATGGCTGGATTTATTAAGATATGCAGTGTTCATACTCCAAGTAGTAATCCAAAGTTGCCTCCTCCTAAACCACTTCCAGGCACTTTAAAGAGGAGGAGACCTCCACAGCCCATTCAGCAACCCCAGCGTCAGCGGCCCCGAGAGAGTTATCAAATGGGACACATGAGACGCTAACTGCAGCTTTTGCCTTGGTTCTTCCTAGTGCCTACAATGGGAAAACTTCACTCCAAAGAGAAACCTATTAAGTCATCATCTCCAAACTAAACCCTCACAAGTAACAGTTGAAGAAAAAATGGCAAGAGATCATATCCTCAGACCAGGTGGAATTACTTAAATTTTAAAGCCTGAAAATTCCAATTTGGGGGTGGGAGGTGGAAAAGGAACCCAATTTTCTTATGAACAGATATTTTTAACTTAATGGCACAAAGTCTTAGAATATTATTATGTGCCCCGTGTTCCCTGTTCTTCGTTGCTGCATTTTCTTCACTTGCAGGCAAACTTGGCTCTCAATAAACTTTTACCACAAATTGAAATAAATATATTTTTTTCAACTGCCAATCAAGGCTAGGAGGCTCGACCACCTCAACATTGGAGACATCACTTGCCAATGTACATACCTTGTTATATGCAGACATGTATTTCTTACGTACACTGTACTTCTGTGTGCAATTGTAAACAGAAATTGCAATATGGATGTTTCTTTGTATTATAAAATTTTTCCGCTCTTAATTAAAAATTACTGTTTAATTGACATACTCAGGATAACAGAGAATGGTGGTATTCAGTGGTCCAGGATTCTGTAATGCTTTACACAGGCAGTTTTGAAATGAAAATCAATTTACCTTTCTGTTACGATGGAGTTGGTTTTGATACTCATTTTTTCTTTATCACATGGCTGCTACGGGCACAAGTGACTATACTGAAGAACACAGTTAAGTGTTGTGCAAACTGGACATAGCAGCACATACTACTTCAGAGTTCATGATGTAGATGTCTGGTTTCTGCTTACGTCTTTTAAACTTTCTAATTCAATTCCATTTTTCAATTAATAGGTGAAATTTTATTCATGCTTTGATAGAAATTATGTCAATGAAATGATTCTTTTTATTTGTAGCCTACTTATTTGTGTTTTTCATATATCTGAAATATGCTAATTATGTTTTCTGTCTGATATGGAAAAGAAAAGCTGTGTCTTTATCAAAATATTTAAACGGTTTTTTCAGCATATCATCACTGATCATTGGTAACCACTAAAGATGAGTAATTTGCTTAAGTAGTAGTTAAAATTGTAGATAGGCCTTCTGACATTTTTTTTCCTAAAATTTTTAACAGCATTGAAGGTGAAACAGCACAATGTCCCATTCCAAATTTATTTTTGAAACAGATGTAAATAATTGGCATTTTAAAGAGAAAGCAAAAACATTTAATGTATTAACAGGCTTATTGCTATGCAGGAAATAGAAGGGGCATTACAAAAATTGAAGCTTGTGACATATTTATTGCTTCTGTTTTCCAACTACATCACTTCAACTAGAAGTAAAGCTATGATTTTCCTGACTTCACATAGGAGGCAAATTTAGAGAAAGTTGTAAAGATTTCTATGTTTTGGGTTTTTTTTTTTCCTTTTTTTTTTTAAGAGTATAAGGTTTACACAATCATTCTCATAATGTGACGCAAGCCAGCAAGGCCAAAAATGCTAGAGAAAATAACGGGATCTCTTCCTTGTAAACTTGTACAGTATGTGGTGACTTTTTCAAAATACAGCTTTTTGTACATGATTTAGAGACAAATTTTGTACATGAAACCCCAGATAGACTATAAATAATTCTAAACAAACAAGTAGGTAGATATGTATGTAATTGCTTTTAAATCATTTAAATGCCTTTGTTTTTGGACTGTGCAAAGGTTGGAAGTGGGTTTGCATTTCTAAAATGGTGACTTTTATTCTGCAAGAGTTCTTAGTAACTTCTTGAGTGTGGTAGACTTTGGAACATGTAAATTTTTTGCTTGTAATGTTATCCTGTGGTAGGATTTTGGCAGGTACACACACTGCCCTATTTTATTTTGAGTCTAAGTTAAATGTTTTCTGAAAAGAGATACATGCACTGAACTCTTTCCACTGCGAATCAAGATGTGGTAATATAAAAGGATCAAGACAAATGAGATCTAATACTACTGTCAGTTTTAATGTCCACTGTGTTTTATACAGTATCTTTTTTTGTTCACTTTGGAAATTTTTACTAAAAATTGCAAAAAATAAAGTATTGTGCAAAGATGTAAGGTTTTTTGAAACTTGAAATGCATTAATAAATAGACGATTAAATCAACTTGAAGGTTCTATACTCTTTGAACTCTGAGAACTATCACAAGAAGCTTCCCACAAGGCAGTGTTTTCTTACAGTTGTCTCTTCCTACAAAAGTATAGATTATCTTTATTCTTAATACTTTGGAATCCATGTAGAAAATTTCCAGTTAGATACTCTGCGTACACACAATAAACCTTTTTAAAACACCCAACTAATCTCAACTGCATTACATTGTTTCTAATCAATATTCAGTGCTTGTCTTGGTGGAAGAGGTGAGTCATTTTGAAAACTTATGGTCTTGTTTTTATGTGTTTTTCAAAGTTTTGAATGCTAAGTACCTCATTTATTTTAAAAAGCCTAGTTTAATGATAAGTTTGTTTAAAATTTTGAGCCATCATTTTTCTCTTCATAGCAAATAAGGAGAGAATTGACATTTCAGTGTTACCTAGAAAAGGAATTGTAAGCCCAGAATAATTCCCTGCATGAGGTAATCTGCTTCAAATTCTTTTTTTAGTCAAGGTTAGCTATAAGTAATACTTGTTAAATGAGTAAATATGTAATACTTTGTGAATTACTTTGTTAATTTAGGAGCATCAAATGTATATTATGTTTAGTTATTTATGAAACTCTCAATATTGATTGATTTGGGTAATTATAAATTAGTTATTTTTACTTGTAATTGAATGCTTAAATTCTGTTTACAGTCCGTCCTCTCTCCCTCCATCCCTCCCTCCCCAGTTTTATAAATTCAGGTACCAATTCACAAACAAAATCAGAAATAAAATAAATTTATTGACTGCTTCTGGATTTAGCATTCCCTGTAGTGTCAAGCAATGTCATGCAGTTTGGGGAAGCATTTATTTAAGGAAATGACAACTTTCTCTGATCAGTCTTGTTTTGTGAGGTGTCTTCAACACTTTATGCTTTGGGTACTTCGTGTTTGTCACAGTCTTAGGATAGTGAAATCTGATTTGTCCAAGCGGAGCAAACTACTCGACCCTCAGTCCTTGTATTTGTCCCTGTAGTAAGACCTAATTATTATTATTTCTTAAAGATGGGATTGGTGTCCTTGGCAACTATGAAATTTCGGGGCTTGTGCATGAGAAGGCATTTCTTATTAAGTATTTCTAATTGAAGGTATCAGAGTGTCAAGCATTACAAACCTGGACAGTTCACCTGGAGGAGTACAAGAAGAGATATTCATTATCCATATTTAAAGGGTCAAGGTTTCCCAAAACCAGGGTGCAAGCCAGATGTAGTTTTAAAGCAGCTGCCAGGGACAGTTCATCTTTAGAGAAGTCACTAAAGTTGTAAGAAATTTTAGTTTCCCCAAAACCACTTTCAACTTCTTAGAAACTAGAAAGACAATTGGTTTGCCCCACAGAGGACAACTTCAGTTTCAGCATCTCTCATGTTGTGTTCTTGATTAAAAACAACTTCCATTTGATATACTTTTCCGTTTATTACCAGTTTAGTTTTTTCACTATTGTTTCTGTATTCAACTCTTTATATGATTAGGATAGAAATTTAGCCCTTCTGTTTTATATTACTATATTGTTTGTGTGTCTTAGATATATACATGTATGTACTATTTTCAGTAGAAATTCATGTATTTTATAATTGGTAAGTTCTTCAGAGCATCTCTTCTATAAAAAGCAACAGGATGCTAGGTAAAACGGAGCATTGAGCAAAATACTGATTAGTTTTTGCTTTTTCCTGAAATCTACACTAAAGTGATAGGGTGTGGGGTAATCCAACAAGGACAAGGTGAATTGAACAAGAACGAAATCTGGAAGCAGATGAAGGAGTACTATTGATTGGGCAGACCCAGGGAAGTCAAATCCTAAACCAGCAGTGGGAACACAACAGAATGGTGTAGTTTGCACTGGTAAGATTTGGGTACCTGGCAGGGCTGGGTGCGGTGGCTCACACCTGTAATCCCAGCACTTTGGGAGGCCAAGGCGGGTGGATCACTTGAGGTCAGGAGTTCGAGACCACCCTGGCCAACATGGTGAAACCCCGTCTCTACTAAAAATACAGCTGGGCGTGGTGGCACATGCTTGTAATCCCAGCTACTCGGGAGGCAGAGGCAGGAGATTTGCTTGAACCCGGGAGGCAGAGGCAGGAGATTTGCTTGAACCCAGGAGGCAGAGGCTGCAGTGAGCCGCGATTGCGCCATTGCACTCCAGCCTGGGTGACAGAGCGAGACTCTGTCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAATTTGAGTACCTGGCCTTTGTTACTTTTTTTCTATGTGTGTGACAAAAACATAATATGCACACTTTTGTAACCCACCTTTCTCATTTAATGGTACATTGATAATGTATATCACATTAACTACTCTAAATATTTCTGTGGATGTATGTTTTTTTTTTTCTTAACCAATTTCCCATTGTTTGGACATGTAGGTTCCACATTGTTTATTATTTTAAACAATTCTAAAGAATTTTAAACAATTCTTAGGAAAATCCTCAGCCTAATAATGAAATTAATTCCTAAAAGTGGAATTGTTGGGGTAAAGGTTTTTTGAGGGACATTGATAAAAATTATGGTACTGTCTCCCAGATAGATGTACCAAGTTATACTACCACGATTTAATATATATATATATATATATTAAATCAGAGTCCCATCCTTAGAAATCCACATATATGCAGCCACATGAATGTATTAGAAACAATAATAGAAGACTCATGCTTAATTCAGTTGATTAGCTTTAGACATAATTCAAATGCAAGTCAAATTGAGTGCCCTAATTGTGGTCTCTTAAGTACCATTTTTCTTCAAGGGAACCAGACTCCTTTGGATAAATCACTAATTCCACCTGTAAGAAAGAAATGTACAAGAAGAACCTAGGAAACATTGTTTTGTACCAGATCAGAAAGATTCAGGAGGCACCTTAGAAGTTACCACTGGCCAAGGCTGAGATAACTTTAGCATCAGCAAGGATAATATCTGCAAGAGATTGAAACTCATAGTATTGTATTTAACTCTGTGAGTTAATGATGGTAGTGGACAGAATTATAGTTACCTTTGGGATACGCTTTTAAAGAAATTCCAGGTAATAAGAGAAATGATAGAATTAGGATATCACCATTTTACCCCCCCAACAATTTATGGATCTAGACAATAATCGCCAGTGACTGCTAACCTCACAAAGTGAGAGCAATCAGATTTTGTGCCTCCTAATGGAAGTACATATACCACCTATGAAGCAGTTCTGCCAAAAGTCACATCTCATCATGATGAAGCCTCCTGATCTAACTACCCCTTCATTAGAAATACAGGGGACAGAGGGACAAATAATATACAAGGGACTCAATCAGCAAAATCCAGACTCTGGAAAACTACAAGACATATGGTCCTGCTTCAACAACAGAAATGCAAAGAGAAAAGACAACGATGGGTTAAAGGAGACTTAAGAGCTACATCTATCAAGACAATTTATGGACTTATTTGGATACTGATTTGAACAAACTGTTGAGACCATTGGAAAAATGTGAAAAGTGGATATTTGATATTAAGGTTTTTAATTATTTTTAGGTGTGATAATGGTATTGTTACATTTTTTAAAGGACCCCTTTTAGAGATGCAAATTGAAACACTTAAAAAATGAAATGATACGATGTATAAGTTTTTGCTTAAAAATAAGGATTGAAGTTGGCTGGTGTGTGTGGATATAGTTGAAACAAGATTGGCTGTGAGTTGATAATTATTGAAGCTGGGTGATGGGCACTTGGGGATTTATTATACTATTTTCTCTACCTGTGTTTATATTTGAAATTTTTCATAGAAGTTTTAAAATGTGGCCAGTTGTGATGGCTCATACCTGTAATCCCAACACTTTGGGAGGCCAAGGTGGGAGGATCACTTGAGCTCAGGAGTTAGAGACCAGCCTGGGCAAAATAGTGAGACTCCATCTCAAAGAAAAAAAAAAAGTGTTTTAAATGTGAATCAAATTCCTATAGAAGCTGATTCATTACTGTTTTTATTTTAGCAGTAATTCATGATAATGACCTGTATTCATAATGATTTTCATAATGATTGTTTTAGTGGAATTAAACTTGAACCAGTCAAGCTAACATAATTATATTCTGCTCCAGTTACAATGAATAATTAATTGATTTCAACTGCTAGGGTGAACTCTTGAAGCTATCAGTCATCCAGCAATCTTAGCAAGCAGGCCATTGGGTCCCTGTTTGCTCTGTCTCTCTCTCTCTCTCTCACTGTTGAAGGGCTTAGCTAACTACTTAAGTAAAATATTTGTTCTCTGTTAAACATGTCAAGGAGTATGGTCAGCTTATCCACATTAAGCCTGTGTGTCCCACGTTGGAGTAAATGTTAAGTAGCTCACTACAATAAACTAGATTCTTCTGCCCTCTCTTGTTTAAATGATCATGTTCCCTGGAGGTGGAAATAGATCTTTAAAAAGATATTCTGTAGTTGTTTGTTCTCAGTGTAAAAAAATGAGAATAATTTGATAAGAGTGTAGGTTGTCTTATATAAAAAGTGGTTCCATTTGCATGAATTTTAGAAAAATCATTTTGGAAAAATGAAGGCTATGTGGTTATACTGAACACATTAAGCAATTTTATTCTTTATTTTAAATGAATATTTTATTATCGTTTTCTTCCCTTGCCCTTTGGGTATGGGAGTTAGCCTTTGTGTTTCTAAATACAACAGGCCGGTTTTTATAAATTAAGGTGTCAATATATTCTTCATTATTTAGTTTTGTGATTGTGGTTAGTTTTCATTTTTCTTAAGTATCTGCTAGTAGCATCTGTAATTAAGTGAAGTGACCTGTTAACCATTTTCCTCTTTCTCCTCCTTTCCTCCTCCTTGAAACATATCAGAGCATGTTTGAAATTCTTTGGCTTTTATGGTATGCATTTGCTGATATGCATTGACCAGTTACCTTACTCACAGATACTTCTTAGGCACTTGATTGTGCCAGGGCCTTGGCTAGATGATAAGAATACAGTAGTGAACTTAACAGTTTCCCTGCCCTGGTGAAGCGTATGGTCTTGTAGGTGAGATAGATATCAGATAATCATGTGAATAAATGTACAATTCCAGCTGTGATACATGCTGAGGAGGAGGTTTTTGGTGATCCAAGAGCTGATCATGCAGAGATAGGACTGAGAAAGGAGGGTGGGACGTTGTCACAGCTGATAATGCAGAGATAGGACTGAGAAAGGAGGGTGGGACATCAGGAAGGTCAGAGAATTCCTTATGAAAGTGATGCTTGAGTCAAAATATGATGGATGAAGAGAGTTTAAATAGATTACATAGAATTTTTAATAATGTCGATTGGTTATATACTGGGCACTGATAGCTGATTTTTCTTTGGGGAAAGGTATGTCAGCCTAGTCATTCAGATTCCTTTATTTTTTTAAATGTTTTTTCATTTTTTGCTTTGCATTGCATTCATTTGCTGAAGAGCTGGCTTGTACTTTGGCAGGTGTCATACTTGGTTATTCTCCTTAGGATATTGGCCCAACAATCTGGGAGTTGTGAAAGGCGCTTCGCTTTTCAGACCTGGGCGTCTGTATCATGACTATCATAAATTTAGGATTAAGACACCTAGCCTCCTACCAGGATGAATGAGGTGTCCATGTGACCTGCTGTGCCCTGGAATTTTATACATCTTTCTCTCATAGCACACACCATATTACAATATAATCCTGCCTCATCTAAGCCAAACTTTCGAGAGAATCATTTACACTCAGTGGCTACTTCAGCTCCCATTCACTTATCAACCTGCTGCAATTTTTCACAGCCCCCAAAGGACTGCAGTCTGTGCCTTCAGGGAGCTGAGGGTCTAGCGGAAGGAAAGAAACCAGCAGTTACAGTACAGAGGGGTTTGTGTTGGAAACTCTACAAACACAGGATGCCCTGGTAGCTCAGAGGAAGTGCATATCGAGCATGGTAGGTAGGTAGTGGGAAGAGCCAAGATGACTTCCCAGAGGAGAAAAGCTGGACCTGAGTTTTGGAGTTTCGGTAAAAGTTTGCTCTAACTAGTCCAAGCTGCTGTCACAAGCTTTTAGAAATGATGTAACCATGGGGCAGTTGACTGTCGTCATGTTCTTTGCTATTTTCATGACTCTGGATGTGCTTTTCCTATTCCCTGGATTGCCCTTTCCCTCGATTCCTCTGCAGGACTGGGCTTTATTAATCTCCATTTCCTTGAGCTTGGCTATAGTAGGTGTTCAATAAACATTTGTTTTGTTGTGTGCTTTGTAAATAGGCAATGAAGCTGATTTCACAAGATAGGCACAAAAGTTAGTTTCATTACAACACATTACCAACAGCTGTATTTTTAACTTTTAACATATCTCATTCTAAATCCTGTGGCAGCACAACCTCCTTCCGTCATACCTGGAGATAAATTTTCTTTCAAAATCTAATATGCACTGTATTTATAGAATATGAAACATACCGACCATGTTTTGCAAAAATGGGAAAGGCATAACTTAGCTTTGGGGCATGTAAGTAACAACTCCTGATAGGAGAAGAAATGTATTCAGAAAGCTCAAATTAGAAATAAAATGGGAGACTCTA (SEQ ID NO: 205) >NP_001101.1 disintegrin and metalloproteinasedomain-containing protein 10 isoform 1 preproprotein [Homo sapiens]MVLLRVLILLLSWAAGMGGQYGNPLNKYIRHYEGLSYNVDSLHQKHQRAKRAVSHEDQFLRLDFHAHGRHFNLRMKRDTSLFSDEFKVETSNKVLDYDTSHIYTGHIYGEEGSFSHGSVIDGRFEGFIQTRGGTFYVEPAERYIKDRTLPFHSVIYHEDDINYPHKYGPQGGCADHSVFERMRKYQMTGVEEVTQIPQEEHAANGPELLRKKRTTSAEKNTCQLYIQTDHLFFKYYGTREAVIAQISSHVKAIDTIYQTTDFSGIRNISFMVKRIRINTTADEKDPTNPFRFPNIGVEKFLELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNTGIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFVESGQPICGNGMVEQGEECDCGYSDQCKDECCFDANQPEGRKCKLKPGKQCSPSQGPCCTAQCAFKSKSEKCRDDSDCAREGICNGFTALCPASDPKPNFTDCNRHTQVCINGQCAGSICEKYGLEECTCASSDGKDDKELCHVCCMKKMDPSTCASTGSVQWSRHFSGRTITLQPGSPCNDFRGYCDVFMRCRLVDADGPLARLKKAIFSPELYENIAEWIVAHWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTLKRRRPPQPIQQPQRQRPRESYQMGHMRR (SEQ ID NO: 206) Transmembrane>NM_001769.4 Homo sapiens CD9 molecule (CD9), domain 2 ortranscript variant 1, mRNA transmembraneAGCCGCCTGCATCTGTATCCAGCGCCAGGTCCCGCCAGTCCCAGCTGCGCGC domain 3 fromGCCCCCCAGTCCCGCACCCGTTCGGCCCAGGCTAAGTTAGCCCTCACCATGC Human CD9CGGTCAAAGGAGGCACCAAGTGCATCAAATACCTGCTGTTCGGATTTAACTTCATCTTCTGGCTTGCCGGGATTGCTGTCCTTGCCATTGGACTATGGCTCCGATTCGACTCTCAGACCAAGAGCATCTTCGAGCAAGAAACTAATAATAATAATTCCAGCTTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATGAT GCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGCATGCTGGGACTGTTCTTCGGCTTCCTCTTGGTGATATTCGCCATTGAAATAGCTGCGGCCATCTGGGGATATTCCCACAAGGATGAGGTGATTAAGGAAGTCCAGGAGTTTTACAAGGACACCTACAACAAGCTGAAAACCAAGGATGAGCCCCAGCGGGAAACGCTGAAAGCCATCCACTATGCGTTGAACTGCTGTGGTTTGGCTGGGGGCGTGGAACAGTTTATCTCAGACATCTGCCCCAAGAAGGACGTACTCGAAACCTTCACCGTGAAGTCCTGTCCTGATGCCATCAAAGAGGTCTTCGACAATAAATTCCACATCATCGGCGCAGTGGGCATCGGCATTGCCGTGGTCATGATATTTGGCATGATCTTCAGTATGATCTTGTGCTGTGCTATCCGCAGGAACCGCGAGATGGTCTAGAGTCAGCTTACATCCCTGAGCAGGAAAGTTTACCCATGAAGATTGGTGGGATTTTTTGTTTGTTTGTTTTGTTTTGTTTGTTGTTTGTTGTTTGTTTTTTTGCCACTAATTTTAGTATTCATTCTGCATTGCTAGATAAAAGCTGAAGTTACTTTATGTTTGTCTTTTAATGCTTCATTCAATATTGACATTTGTAGTTGAGCGGGGGGTTTGGTTTGCTTTGGTTTATATTTTTTCAGTTGTTTGTTTTTGCTTGTTATATTAAGCAGAAATCCTGCAATGAAAGGTACTATATTTGCTAGACTCTAGACAAGATATTGTACATAAAAGAATTTTTTTGTCTTTAAATAGATACAAATGTCTATCAACTTTAATCAAGTTGTAACTTATATTGAAGACAATTTGATACATAATAAAAAATTATGACAATGTCCTGGA (SEQ ID NO: 207)>NP_001760.1 CD9 antigen isoform 1 [Homo sapiens]MPVKGGTKCIKYLLFGFNFIFWLAGIAVLAIGLWLRFDSQTKSIFEQETNNNNSSFYTGVYILIGAGALMMLVGFL GCCGAVQESQCMLGLFFGFLLVIFAIEIAAAIWGYSHKDEVIKEVQEFYKDTYNKLKTKDEPQRETLKAIHYALNCCGLAGGVEQFISDICPKKDVLETFTVKSCPDAIKEVFDNKFHIIGAVGIGIAVVMIFGMIFSMILCCAIRRNREMV (SEQ ID NO: 208) Human CD298>NM_001679.4 Homo sapiens ATPase Na+/K+ transportingsubunit beta 3 (ATP1B3), mRNAAGTCGGCTCGAGTACTCCCCGTAACGAGGAGGTGTTCTCGGCCGTCCCACCCTTCACTGCCGTCTCCGGGCTGCGCCGCCGGAGCCGGGACGCGCCTCCGCAGCCCTCGCCGCCTCCATCCCCGCGGCCGCAGCTCCTCTCGCCGTCCGCGCGCACACCATGACGAAGAACGAGAAGAAGTCCCTCAACCAGAGCCTGGCCGAGTGGAAGCTCTTCATCTACAACCCGACCACCGGAGAATTCCTGGGGCGCACCGCCAAGAGCTGGGGTTTGATCTTGCTCTTCTACCTAGTTTTTTATGGGTTCCTGGCTGCACTCTTCTCATTCACGATGTGGGTTATGCTTCAGACTCTCAACGATGAGGTTCCAAAATACCGTGACCAGATTCCTAGCCCAGGACTCATGGTTTTTCCAAAACCAGTGACCGCATTGGAATATACATTCAGTAGGTCTGATCCAACTTCGTATGCAGGGTACATTGAAGACCTTAAGAAGTTTCTAAAACCATATACTTTAGAAGAACAGAAGAACCTCACAGTCTGTCCTGATGGAGCACTTTTTGAACAGAAGGGTCCAGTTTATGTTGCATGTCAGTTTCCTATTTCATTACTTCAAGCATGCAGTGGTATGAATGATCCTGATTTTGGCTATTCTCAAGGAAACCCTTGTATTCTTGTGAAAATGAACAGAATAATTGGATTAAAGCCTGAAGGAGTGCCAAGGATAGATTGTGTTTCAAAGAATGAAGATATACCAAATGTAGCAGTTTATCCTCATAATGGAATGATAGACTTAAAATATTTCCCATATTATGGGAAAAAACTGCATGTTGGGTATCTACAGCCATTGGTTGCTGTTCAGGTCAGCTTTGCTCCTAACAACACTGGGAAAGAAGTAACAGTTGAGTGCAAGATTGATGGATCAGCCAACCTAAAAAGTCAGGATGATCGTGACAAGTTTTTGGGACGAGTTATGTTCAAAATCACAGCACGTGCATAGTATGAGTAGGATATCTCCACAGAGTAAATGTTGTGTTGTCTGTCTTCATTTTGTAACAGCTGGACCTTCCATTCTAGAATTATGAGACCACCTTGGAGAAAGGTGTGTGGTACATGACATTGGGTTACATCATAACGTGCTTCCAGATCATAGTGTTCAGTGTCCTCTGAAGTAACTGCCTGTTGCCTCTGCTGCCCTTTGAACCAGTGTACAGTCGCCAGATAGGGACCGGTGAACACCTGATTCCAAACATGTAGGATGGGGGTCTTGTCCTCTTTTTATGTGGTTTAATTGCCAAGTGTCTAAAGCTTAATATGCCGTGCTATGTAAATATTTTATGGATATAACAACTGTCATATTTTGATGTCAACAGAGTTTTAGGGATAAAATGGTACCCGGCCAACATCAAGTGACTTTATAGCTGCAAGAAATGTGGTATGTGGAGAAGTTCTGTATGTGAGGAAGGAAAAAAAGAAAATAAAAGTGTGTTTGAAAAATATTATCTTGGGTTCTTTGTAAAATTTATTTTTTACATGCTGAATTAGCCTCGATCTTTTTGATTAAGAGCACAAACTTTTTTTTGTAAAACATGTAAAAAAAAAAACTGGGATTAATTTTTAGTGTTGGAACTGCCTCTTATTTTAGGCTGTAGATAAAATAGCATTTTTAGGTTAGCCAGTGTGACTATGCACCTAATTTTTTATGAGATTAAATTCATAAGACTTAATTTGTACAATAGTTTGTGAAATATCTTGTTACTGCTTTTATTTAGCAGACTGTGGACTGTAATAAAGTATATAAATTGTGAAATATAAAAACTTGGAACTTATTCAAAGCTTCAAAGCAAA (SEQ ID NO: 209) >NP_001670.1 sodium/potassium-transporting ATPasesubunit beta-3 [Homo sapiens]MTKNEKKSLNQSLAEWKLFIYNPTTGEFLGRTAKSWGLILLFYLVFYGFLAALFSFTMWVMLQTLNDEVPKYRDQIPSPGLMVFPKPVTALEYTFSRSDPTSYAGYIEDLKKFLKPYTLEEQKNLTVCPDGALFEQKGPVYVACQFPISLLQACSGMNDPDFGYSQGNPCILVKMNRIIGLKPEGVPRIDCVSKNEDIPNVAVYPHNGMIDLKYFPYYGKKLHVGYLQPLVAVQVSFAPNNTGKEVTVECKIDGSANLKSQDDRDKFLGRVMFKITARA (SEQ ID NO: 210) Lipid affinity tag>NM_004985.5 Homo sapiens KRAS proto-oncogene, modified fromGTPase (KRAS), transcript variant b, mRNA Human KRASCTAGGCGGCGGCCGCGGCGGCGGAGGCAGCAGCGGCGGCGGCAGTGGCGGCGGCGAAGGTGGCGGCGGCTCGGCCAGTACTCCCGGCCCCCGCCATTTCGGACTGGGAGCGAGCGCGGCGCAGGCACTGAAGGCGGCGGCGGGGCCAGAGGCTCAGCGGCTCCCAGGTGCGGGAGAGAGGCCTGCTGAAAATGACTGAATATAAACTTGTGGTAGTTGGAGCTGGTGGCGTAGGCAAGAGTGCCTTGACGATACAGCTAATTCAGAATCATTTTGTGGACGAATATGATCCAACAATAGAGGATTCCTACAGGAAGCAAGTAGTAATTGATGGAGAAACCTGTCTCTTGGATATTCTCGACACAGCAGGTCAAGAGGAGTACAGTGCAATGAGGGACCAGTACATGAGGACTGGGGAGGGCTTTCTTTGTGTATTTGCCATAAATAATACTAAATCATTTGAAGATATTCACCATTATAGAGAACAAATTAAAAGAGTTAAGGACTCTGAAGATGTACCTATGGTCCTAGTAGGAAATAAATGTGATTTGCCTTCTAGAACAGTAGACACAAAACAGGCTCAGGACTTAGCAAGAAGTTATGGAATTCCTTTTATTGAAACATCAGCAAAGACAAGACAGGGTGTTGATGATGCCTTCTATACATTAGTTCGAGAAATTCGAAAACATAAAGAAAAGATGAGCAAAGATGGTAAAAAGAAGAAAAAGAAGTCAAAGACAAAGTGTGTAATTATGTAAATACAATTTGTACTTTTTTCTTAAGGCATACTAGTACAAGTGGTAATTTTTGTACATTACACTAAATTATTAGCATTTGTTTTAGCATTACCTAATTTTTTTCCTGCTCCATGCAGACTGTTAGCTTTTACCTTAAATGCTTATTTTAAAATGACAGTGGAAGTTTTTTTTTCCTCTAAGTGCCAGTATTCCCAGAGTTTTGGTTTTTGAACTAGCAATGCCTGTGAAAAAGAAACTGAATACCTAAGATTTCTGTCTTGGGGCTTTTGGTGCATGCAGTTGATTACTTCTTATTTTTCTTACCAATTGTGAATGTTGGTGTGAAACAAATTAATGAAGCTTTTGAATCATCCCTATTCTGTGTTTTATCTAGTCACATAAATGGATTAATTACTAATTTCAGTTGAGACCTTCTAATTGGTTTTTACTGAAACATTGAGGGAACACAAATTTATGGGCTTCCTGATGATGATTCTTCTAGGCATCATGTCCTATAGTTTGTCATCCCTGATGAATGTAAAGTTACACTGTTCACAAAGGTTTTGTCTCCTTTCCACTGCTATTAGTCATGGTCACTCTCCCCAAAATATTATATTTTTTCTATAAAAAGAAAAAAATGGAAAAAAATTACAAGGCAATGGAAACTATTATAAGGCCATTTCCTTTTCACATTAGATAAATTACTATAAAGACTCCTAATAGCTTTTCCTGTTAAGGCAGACCCAGTATGAAATGGGGATTATTATAGCAACCATTTTGGGGCTATATTTACATGCTACTAAATTTTTATAATAATTGAAAAGATTTTAACAAGTATAAAAAATTCTCATAGGAATTAAATGTAGTCTCCCTGTGTCAGACTGCTCTTTCATAGTATAACTTTAAATCTTTTCTTCAACTTGAGTCTTTGAAGATAGTTTTAATTCTGCTTGTGACATTAAAAGATTATTTGGGCCAGTTATAGCTTATTAGGTGTTGAAGAGACCAAGGTTGCAAGGCCAGGCCCTGTGTGAACCTTTGAGCTTTCATAGAGAGTTTCACAGCATGGACTGTGTCCCCACGGTCATCCAGTGTTGTCATGCATTGGTTAGTCAAAATGGGGAGGGACTAGGGCAGTTTGGATAGCTCAACAAGATACAATCTCACTCTGTGGTGGTCCTGCTGACAAATCAAGAGCATTGCTTTTGTTTCTTAAGAAAACAAACTCTTTTTTAAAAATTACTTTTAAATATTAACTCAAAAGTTGAGATTTTGGGGTGGTGGTGTGCCAAGACATTAATTTTTTTTTTAAACAATGAAGTGAAAAAGTTTTACAATCTCTAGGTTTGGCTAGTTCTCTTAACACTGGTTAAATTAACATTGCATAAACACTTTTCAAGTCTGATCCATATTTAATAATGCTTTAAAATAAAAATAAAAACAATCCTTTTGATAAATTTAAAATGTTACTTATTTTAAAATAAATGAAGTGAGATGGCATGGTGAGGTGAAAGTATCACTGGACTAGGAAGAAGGTGACTTAGGTTCTAGATAGGTGTCTTTTAGGACTCTGATTTTGAGGACATCACTTACTATCCATTTCTTCATGTTAAAAGAAGTCATCTCAAACTCTTAGTTTTTTTTTTTTACAACTATGTAATTTATATTCCATTTACATAAGGATACACTTATTTGTCAAGCTCAGCACAATCTGTAAATTTTTAACCTATGTTACACCATCTTCAGTGCCAGTCTTGGGCAAAATTGTGCAAGAGGTGAAGTTTATATTTGAATATCCATTCTCGTTTTAGGACTCTTCTTCCATATTAGTGTCATCTTGCCTCCCTACCTTCCACATGCCCCATGACTTGATGCAGTTTTAATACTTGTAATTCCCCTAACCATAAGATTTACTGCTGCTGTGGATATCTCCATGAAGTTTTCCCACTGAGTCACATCAGAAATGCCCTACATCTTATTTCCTCAGGGCTCAAGAGAATCTGACAGATACCATAAAGGGATTTGACCTAATCACTAATTTTCAGGTGGTGGCTGATGCTTTGAACATCTCTTTGCTGCCCAATCCATTAGCGACAGTAGGATTTTTCAAACCTGGTATGAATAGACAGAACCCTATCCAGTGGAAGGAGAATTTAATAAAGATAGTGCTGAAAGAATTCCTTAGGTAATCTATAACTAGGACTACTCCTGGTAACAGTAATACATTCCATTGTTTTAGTAACCAGAAATCTTCATGCAATGAAAAATACTTTAATTCATGAAGCTTACTTTTTTTTTTTGGTGTCAGAGTCTCGCTCTTGTCACCCAGGCTGGAATGCAGTGGCGCCATCTCAGCTCACTGCAACCTCCATCTCCCAGGTTCAAGCGATTCTCGTGCCTCGGCCTCCTGAGTAGCTGGGATTACAGGCGTGTGCCACTACACTCAACTAATTTTTGTATTTTTAGGAGAGACGGGGTTTCACCCTGTTGGCCAGGCTGGTCTCGAACTCCTGACCTCAAGTGATTCACCCACCTTGGCCTCATAAACCTGTTTTGCAGAACTCATTTATTCAGCAAATATTTATTGAGTGCCTACCAGATGCCAGTCACCACACAAGGCACTGGGTATATGGTATCCCCAAACAAGAGACATAATCCCGGTCCTTAGGTAGTGCTAGTGTGGTCTGTAATATCTTACTAAGGCCTTTGGTATACGACCCAGAGATAACACGATGCGTATTTTAGTTTTGCAAAGAAGGGGTTTGGTCTCTGTGCCAGCTCTATAATTGTTTTGCTACGATTCCACTGAAACTCTTCGATCAAGCTACTTTATGTAAATCACTTCATTGTTTTAAAGGAATAAACTTGATTATATTGTTTTTTTATTTGGCATAACTGTGATTCTTTTAGGACAATTACTGTACACATTAAGGTGTATGTCAGATATTCATATTGACCCAAATGTGTAATATTCCAGTTTTCTCTGCATAAGTAATTAAAATATACTTAAAAATTAATAGTTTTATCTGGGTACAAATAAACAGGTGCCTGAACTAGTTCACAGACAAGGAAACTTCTATGTAAAAATCACTATGATTTCTGAATTGCTATGTGAAACTACAGATCTTTGGAACACTGTTTAGGTAGGGTGTTAAGACTTACACAGTACCTCGTTTCTACACAGAGAAAGAAATGGCCATACTTCAGGAACTGCAGTGCTTATGAGGGGATATTTAGGCCTCTTGAATTTTTGATGTAGATGGGCATTTTTTTAAGGTAGTGGTTAATTACCTTTATGTGAACTTTGAATGGTTTAACAAAAGATTTGTTTTTGTAGAGATTTTAAAGGGGGAGAATTCTAGAAATAAATGTTACCTAATTATTACAGCCTTAAAGACAAAAATCCTTGTTGAAGTTTTTTTAAAAAAAGCTAAATTACATAGACTTAGGCATTAACATGTTTGTGGAAGAATATAGCAGACGTATATTGTATCATTTGAGTGAATGTTCCCAAGTAGGCATTCTAGGCTCTATTTAACTGAGTCACACTGCATAGGAATTTAGAACCTAACTTTTATAGGTTATCAAAACTGTTGTCACCATTGCACAATTTTGTCCTAATATATACATAGAAACTTTGTGGGGCATGTTAAGTTACAGTTTGCACAAGTTCATCTCATTTGTATTCCATTGATTTTTTTTTTCTTCTAAACATTTTTTCTTCAAACAGTATATAACTTTTTTTAGGGGATTTTTTTTTAGACAGCAAAAACTATCTGAAGATTTCCATTTGTCAAAAAGTAATGATTTCTTGATAATTGTGTAGTAATGTTTTTTAGAACCCAGCAGTTACCTTAAAGCTGAATTTATATTTAGTAACTTCTGTGTTAATACTGGATAGCATGAATTCTGCATTGAGAAACTGAATAGCTGTCATAAAATGAAACTTTCTTTCTAAAGAAAGATACTCACATGAGTTCTTGAAGAATAGTCATAACTAGATTAAGATCTGTGTTTTAGTTTAATAGTTTGAAGTGCCTGTTTGGGATAATGATAGGTAATTTAGATGAATTTAGGGGAAAAAAAAGTTATCTGCAGATATGTTGAGGGCCCATCTCTCCCCCCACACCCCCACAGAGCTAACTGGGTTACAGTGTTTTATCCGAAAGTTTCCAATTCCACTGTCTTGTGTTTTCATGTTGAAAATACTTTTGCATTTTTCCTTTGAGTGCCAATTTCTTACTAGTACTATTTCTTAATGTAACATGTTTACCTGGAATGTATTTTAACTATTTTTGTATAGTGTAAACTGAAACATGCACATTTTGTACATTGTGCTTTCTTTTGTGGGACATATGCAGTGTGATCCAGTTGTTTTCCATCATTTGGTTGCGCTGACCTAGGAATGTTGGTCATATCAAACATTAAAAATGACCACTCTTTTAATTGAAATTAACTTTTAAATGTTTATAGGAGTATGTGCTGTGAAGTGATCTAAAATTTGTAATATTTTTGTCATGAACTGTACTACTCCTAATTATTGTAATGTAATAAAAATAGTTACAGTG AC (SEQ ID NO: 211)>NP_004976.2 GTPase KRas isoform b [Homo sapiens]MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRKHKEKMSKDGKKKKKKSKTKCVIM (SEQ ID NO: 212) >Lipid affinity tag nucleotide sequenceAAAAAGAAGAAAAAGAAGAAGAAGACAAAGTGTGTAATTATG (SEQ IDNO: 213) >Lipid affinity tag peptide sequenceKKKKKKKKTKCVIM (SEQ ID NO: 214) Myr/Palm tag>NM_002356.7 Homo sapiens myristoylated alanine rich modified fromprotein kinase C substrate (MARCKS), mRNA Human MARCKSGCACTTGGGCGTTGGACCCCGCATCTTATTAGCAACCAGGGAGATTTCTCCATTTTCCTCTTGTCTACAGTGCGGCTACAAATCTGGGATTTTTTTATTACTTCTTTTTTTTTCGAACTACACTTGGGCTCCTTTTTTTGTGCTCGACTTTTCCACCCTTTTTCCCTCCCTCCTGTGCTGCTGCTTTTTGATCTCTTCGACTAAAATTTTTTTATCCGGAGTGTATTTAATCGGTTCTGTTCTGTCCTCTCCACCACCCCCACCCCCCTCCCTCCGGTGTGTGTGCCGCTGCCGCTGTTGCCGCCGCCGCTGCTGCTGCTGCTCGCCCCGTCGTTACACCAACCCGAGGCTCTTTGTTTCCCCTCTTGGATCTGTTGAGTTTCTTTGTTGAAGAAGCCAGCATGGGTGCCCAGTTCTCCAAGACCGCAGCGAAGGGAGAAGCCGCCGCGGAGAGGCCTGGGGAGGCGGCTGTGGCCTCGTCGCCTTCCAAAGCGAACGGACAGGAGAATGGCCACGTGAAGGTAAACGGCGACGCTTCGCCCGCGGCCGCCGAGTCGGGCGCCAAGGAGGAGCTGCAGGCCAACGGCAGCGCCCCGGCCGCCGACAAGGAGGAGCCCGCGGCCGCCGGGAGCGGGGCGGCGTCGCCCTCCGCGGCCGAGAAAGGTGAGCCGGCCGCCGCCGCTGCCCCCGAGGCCGGGGCCAGCCCGGTAGAGAAGGAGGCCCCCGCGGAAGGCGAGGCTGCCGAGCCCGGCTCGCCCACGGCCGCGGAGGGAGAGGCCGCGTCGGCCGCCTCCTCGACTTCTTCGCCCAAGGCCGAGGACGGGGCCACGCCCTCGCCCAGCAACGAGACCCCGAAAAAAAAAAAGAAGCGCTTTTCCTTCAAGAAGTCTTTCAAGCTGAGCGGCTTCTCCTTCAAGAAGAACAAGAAGGAGGCTGGAGAAGGCGGTGAGGCTGAGGCGCCCGCTGCCGAAGGCGGCAAGGACGAGGCCGCCGGGGGCGCAGCTGCGGCCGCCGCCGAGGCGGGCGCGGCCTCCGGGGAGCAGGCAGCGGCGCCGGGCGAGGAGGCGGCAGCGGGCGAGGAGGGGGCGGCGGGTGGCGACCCGCAGGAGGCCAAGCCCCAGGAGGCCGCTGTCGCGCCAGAGAAGCCGCCCGCCAGCGACGAGACCAAGGCCGCCGAGGAGCCCAGCAAGGTGGAGGAGAAAAAGGCCGAGGAGGCCGGGGCCAGCGCCGCCGCCTGCGAGGCCCCCTCCGCCGCCGGGCCCGGCGCGCCCCCGGAGCAGGAGGCAGCCCCCGCGGAGGAGCCCGCGGCCGCCGCAGCCTCGTCAGCCTGCGCAGCCCCCTCACAGGAGGCCCAGCCCGAGTGCAGTCCAGAAGCCCCCCCAGCGGAGGCGGCAGAGTAAAAGAGCAAGCTTTTGTGAGATAATCGAAGAACTTTTCTCCCCCGTTTGTTTGTTGGAGTGGTGCCAGGTACTGGTTTTGGAGAACTTGTCTACAACCAGGGATTGATTTTAAAGATGTCTTTTTTTATTTTACTTTTTTTTAAGCACCAAATTTTGTTGTTTTTTTTTTTTCTCCCCTCCCCACAGATCCCATCTCAAATCATTCTGTTAACCACCATTCCAACAGGTCGAGGAGAGCTTAAACACCTTCTTCCTCTGCCTTGTTTCTCTTTTATTTTTTATTTTTTCGCATCAGTATTAATGTTTTTGCATACTTTGCATCTTTATTCAAAAGTGTAAACTTTCTTTGTCAATCTATGGACATGCCCATATATGAAGGAGATGGGTGGGTCAAAAAGGGATATCAAATGAAGTGATGGGGTCACAATGGGGAAATTGAAGTGGTGCATAACATTGCCAAAATAGTGTGCCACTAGAAATGGTGTAAAGGCTGTCTTTTTTTTTTTTTTAAAAGAAAAGTTATTACCATGTATTTTGTGAGGCAGGTTTACAACACTACAAGTCTTGAGTTAAGAAGGAAAGAGGAAAAAAGAAAAAACACCAATACCCAGATTTAAAAAAAAAAAAACGATCATAGTCTTAGGAGTTCATTTAAACCATAGGAACTTTTCACTTATCTCATGTTAGCTGTACCAGTCAGTGATTAAGTAGAACTACAAGTTGTATAGGCTTTATTGTTTATTGCTGGTTTATGACCTTAATAAAGTGTAATTATGTATTACCAGCAGGGTGTTTTTAACTGTGACTATTGTATAAAAACAAATCTTGATATCCAGAAGCACATGAAGTTTGCAACTTTCCACCCTGCCCATTTTTGTAAAACTGCAGTCATCTTGGACCTTTTAAAACACAAATTTTAAACTCAACCAAGCTGTGATAAGTGGAATGGTTACTGTTTATACTGTGGTATGTTTTTGATTACAGCAGATAATGCTTTCTTTTCCAGTCGTCTTTGAGAATAAAGGAAAAAAAATCTTCAGATGCAATGGTTTTGTGTAGCATCTTGTCTATCATGTTTTGTAAATACTGGAGAAGCTTTGACCAATTTGACTTAGAGATGGAATGTAACTTTGCTTACAAAAATTGCTATTAAACTCCTGCTTAAGGTGTTCTAATTTTCTGTGAGCACACTAAAAGCGAAAAATAAATGTGAATAAAATGTACAAATTTGTTGTGTTTTTTTATGTTCTAATAATACTGAGACTTCTAGGTCTTAGGTTAATTTTTAGGAAGATCTTGCATGCCATCAGGAGTAAATTTTATTGTGGTTCTTAATCTGAAGTTTTCAAGCTCTGAAATTCATAATCCGCAGTGTCAGATTACGTAGAGGAAGATCTTACAACATTTCCATGTCAAATCTGTTACCATTTATTGGCATTTAGTTTTCATTTAAGAATTGAACATAATTATTTTTATTGTAGCTATATAGCATGTCAGATTAAATCATTTACAACAAAAGGGGTGTGAACCTAAGACTATTTAAATGTCTTATGAGAAAATTTCATAAAGCCATTCTCTTGTCATTCAGGTCCAGAAACAAATTTTAAACTGAGTGAGAGTCTATAGAATCCATACTGCAGATGGGTCATGAAATGTGACCAAATGTGTTTCAAAAATTGATGGTGTATTACCTGCTATTGTAATTGCTTAGTGCTTGGCTAATTTCCAAATTATTGCATAATATGTTCTACCTTAAGAAAACAGGTTTATGTAACAAAGTAATGGTGTTGAATGGATGATGTCAGTTCATGGGCCTTTAGCATAGTTTTAAGCATCCTTTTTTTTTTTTTTTTTTGAAAGTGTGTTAGCATCTTGTTACTCAAAGGATAAGACAGACAATAATACTTCACTGAATCTTAATAATCTTTACTAGTTTACCTCCTCTGCTCTTTGCCACCCGATAACTGGATATCTTTTCCTTCAAAGGACCCTAAACTGATTGAAATTTAAGATATGTATCAAAAACATTATTTCATTTAATGCACATCTGTTTTGCTGTTTTTGAGCAGTGTGCAGTTTAGGGTTCATGATAAATCATTGAACCACATGTGTAACAACTGAATGCCAAATCTTAAACTCATTAGAAAAATAACAAATTAGGTTTTGACACGCATTCTTAATTGGAATAATGGATCAAAAATAGTGGTTCATGACCTTACCAAACACCCTTGCTACTAATAAAATCAAATAACACTTAGAAGGGTATGTATTTTTAGTTAGGGTTTCTTGATCTTGGAGGATGTTTGAAAGTTAAAAATTGAATTTGGTAACCAAAGGACTGATTTATGGGTCTTTCCTATCTTAACCAACGTTTTCTTAGTTACCTAGATGGCCAAGTACAGTGCCTGGTATGTAGTAAGACTCAGTAAAAAAGTGGATTTTTAAAAATAACTCCCAAAGTGAATAGTCAAAAATCCTGTTAGCAAACTGTTATATATTGCTAAGTTTGTTCTTTTAACAGCTGGAATTTATTAAGATGCATTATTTTGATTTTATTCACTGCCTAAAACACTTTGGGTGGTATTGATGGAGTTGGTGGATTTTCCTCCAAGTGATTAAATGAAATTTGACGTATCTTTTCATCCAAAGTTTTGTACATCATGTTTTCTAACGGAAAAAAATGTTAATATGGCTTTTTTGTATTACTAAAAATAGCTTTGAGATTAAGGAAAAATAAATAACTCTTGTACAGTTCAGTATTGTCTATTAAATCTGTATTGGCAGTATGTATAATGGCATTTGCTGTGGTTACAAAATACTTCCTCTGGGTTATAATAATCATTTGATCCAATTCCTATTGCTTGTAAAATAAAGTTTTACCAGTTGATATAATCAA (SEQ ID NO: 215) >NP_002347.5 myristoylated alanine-rich C-kinasesubstrate [Homo sapiens]MGAQFSKTAAKGEAAAERPGEAAVASSPSKANGQENGHVKVNGDASPAAAESGAKEELQANGSAPAADKEEPAAAGSGAASPSAAEKGEPAAAAAPEAGASPVEKEAPAEGEAAEPGSPTAAEGEAASAASSTSSPKAEDGATPSPSNETPKKKKKRFSFKKSFKLSGFSFKKNKKEAGEGGEAEAPAAEGGKDEAAGGAAAAAAEAGAASGEQAAAPGEEAAAGEEGAAGGDPQEAKPQEAAVAPEKPPASDETKAAEEPSKVEEKKAEEAGASAAACEAPSAAGPGAPPEQEAAPAEEPAAAAASSACAAPSQEAQPECSPEAPPAEAAE (SEQ ID NO: 216) >Myr/Palm tag modified from Human MARCKS, nucleotidesequenceATGGGTTGCTGTTTCTCCAAGACC (SEQ ID NO: 217) >Myr/Palm tag modified from Human MARCKS, peptidesequence MGCCFSKT (SEQ ID NO: 218)

In some embodiments of any of the aspects provided herein, the fusionpolypeptide further comprises a peptide linker. The linker may beflexible, rigid, or cleavable. Further, the linker can be linkeddirectly or via another linker (e.g., a peptide of one, two, three,four, five, six, seven, eight, nine, ten or more amino acids) to thefusion polypeptides described herein. Linkers can be configuredaccording to a specific need, e.g., based on at least one of thefollowing characteristics. In some embodiments of any of the aspects,linkers can be configured to have a sufficient length and flexibilitysuch that it can allow for a cleavage at a target site. In someembodiments of any of the aspects, linkers can be configured to allowmultimerization of the fusion polypeptides provided herein. In someembodiments of any of the aspects, linkers can be configured tofacilitate expression and purification of the fusion proteins orengineered extracellular vesicles provided herein.

In some embodiments of any of the aspects, a linker can be configured tohave any length in a form of a peptide, peptidomimetic, an aptamer, aprotein, a nucleic acid (e.g., DNA or RNA), or any combinations thereof.For example, in one embodiment, the linker may be a polypeptide linkersuch as Gly-Ser-Ser-Gly or a variation thereof as known by one ofordinary skill in the art. In another embodiment the linker may be aprotein sequence for a self-cleavable peptide. For example, 2A sequencessuch as P2A, E2A, F2A, and T2A code for self-cleavable peptides byinducing ribosomal slippage on the mRNA at the 2A site which preventspeptide bond formation. The slippage will result in two separatepeptides after translation. This allows the expression of two separateproteins from one promoter region. Any combination of the proteinsdescribed herein may be expressed with a self-cleavable peptide as knownby one of ordinary skill in the art.

In some embodiments of any of the aspects, the polypeptide linker is anon-cleavable linker. In some embodiments of any of the aspects, alinker can be a chemical linker of any length.

In some embodiments of any of the aspects, the linker is an Fc linker.An exemplary nucleic acid sequence encoding an Fc polypeptide is:

>KY053479.1 Synthetic construct Fc-adiponectin gene, complete cds(SEQ ID NO: 219) ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTCACGAACTCGATATCGGCCATGGTTAGATCTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAGCCAGCGGAAGTGGCGGAGGAGGCGGTCCTGGAGAAGGTGCCTATGTATACCGCTCAGCATTCAGTGTGGGATTGGAGACTTACGTTACTATCCCCAACATGCCCATTCGCTTTACCAAGATCTTCTACAATCAGCAAAACCACTATGATGGCTCCACTGGTAAATTCCACTGCAACATTCCTGGGCTGTACTACTTTGCCTACCACATCACAGTCTATATGAAGGATGTGAAGGTCAGCCTCTTCAAGAAGGACAAGGCTATGCTCTTCACCTATGATCAGTACCAGGAAAATAATGTGGACCAGGCCTCCGGCTCTGTGCTCCTGCATCTGGAGGTGGGCGACCAAGTCTGGCTCCAGGTGTATGGGGAAGGAGAGCGTAATGGACTCTATGCTGATAATGACAATGACTCCACCTTCACAGGCTTTCTTCTCTACCATGACACCAACTCTAGAAAGCTTCCTGGAGAAGGTGCCTATGTATACCGCTCAGCATTCAGTGTGGGATTGGAGACTTACGTTACTATCCCCAACATGCCCATTCGCTTTACCAAGATCTTCTACAATCAGCAAAACCACTATGATGGCTCCACTGGTAAATTCCACTGCAACATTCCTGGGCTGTACTACTTTGCCTACCACATCACAGTCTATATGAAGGATGTGAAGGTCAGCCTCTTCAAGAAGGACAAGGCTATGCTCTTCACCTATGATCAGTACCAGGAAAATAATGTGGACCAGGCCTCCGGCTCTGTGCTCCTGCATCTGGAGGTGGGCGACCAAGTCTGGCTCCAGGTGTATGGGGAAGGAGAGCGTAATGGACTCTATGCTGATAATGACAATGACTCCACCTTCACAGGCTTTCTTCTCTACCATGACACCAACACTAGTCCTGGAGAAGGTGCCTATGTATACCGCTCAGCATTCAGTGTGGGATTGGAGACTTACGTTACTATCCCCAACATGCCCATTCGCTTTACCAAGATCTTCTACAATCAGCAAAACCACTATGATGGCTCCACTGGTAAATTCCACTGCAACATTCCTGGGCTGTACTACTTTGCCTACCACATCACAGTCTATATGAAGGATGTGAAGGTCAGCCTCTTCAAGAAGGACAAGGCTATGCTCTTCACCTATGATCAGTACCAGGAAAATAATGTGGACCAGGCCTCCGGCTCTGTGCTCCTGCATCTGGAGGTGGGCGACCAAGTCTGGCTCCAGGTGTATGGGGAAGGAGAGCGTAATGGACTCTATGCTGATAATGACAATGACTCCACCTTCACAGGCTTTCTTCTCTACCATGACACCAACTAA.The amino acid sequence of the Fc linker is:

>Fc Translation (SEQ ID NO: 220)DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK.

In some embodiments of any of the aspects, the linker is a P2A peptidelinker. P2A is a self-cleaving peptide sequence allowing for expressionof two proteins from one promoter. In some embodiments, the P2A linkeris encoded by the nucleic acid sequence:

(SEQ ID NO: 221) GCTACTAACTTCAGCCTGCTGAAGCAG.The amino acid sequence of P2A is

(SEQ ID No: 222) ATNFSLKQAGDVENPGP.

In some embodiments of any of the aspects, the linker is provides amultimerization (e.g., dimerization) domain wherein one fusionpolypeptide may connect with another fusion polypeptide at each fusionpolypeptide's respective multimerization domain. Multimerization ofmultiple fusion polypeptides will provide multiple fusion polypeptideswithin close proximity to one another to one or more a target receptoron the target cell, wherein the multiple fusion peptides will enhancereceptor clustering on the target cell. Clustering receptors on a targetcell will result in enhanced signal transduction. Without receptorclustering a signal may be weaker or not occur all together. Forexample, Fc domain sequences presented herein dimerize resulting in twofusion polypeptides connected by a covalent bond via the two Fc domainson their respective fusion polypeptide. One preferred embodiment of anFc domain is from IgG4, herein labeled 4Fc. In other embodiments Fc maybe from IgG1, herein labeled Fc. In certain embodiments Fc from otherimmunoglobulin, (e.g., IgG2, IgG3, etc.) may be used.

Additional non-limiting examples of linkers that can be used and theirproperties are further described in detail, e.g., in Chen X, Zaro J L,Shen W C. Fusion protein linkers: property, design and functionality.Adv Drug Deliv Rev. 2013; 65(10):1357-1369.doi:10.1016/j.addr.2012.09.039; O'Shea E K, Lumb K J, Kim P S. Peptide‘Velcro’: design of a heterodimeric coiled coil. Curr Biol. 1993 Oct. 1;3(10):658-67. doi: 10.1016/0960-9822(93)90063-t. PMID: 15335856; andMüller K M, Arndt K M, Alber T. Protein fusions to coiled-coil domains.Methods Enzymol. 2000; 328:261-82. doi: 10.1016/s0076-6879(00)28402-4.PMID: 11075350, the contents of which are incorporated herein byreference in their entireties.

The engineered extracellular vesicle compositions provided herein cancomprise variations in the configuration of the POI domain, linkers,and/or vesicle targeting domain. The specific combination andlocalization of these domains can enhance fusion polypeptide anchoring,function, or therapeutic effect, e.g., modulating inflammation.

Thus, in one aspect, provided herein is an engineered extracellularvesicle comprising: at least one fusion polypeptide comprising: (i) atleast one protein of interest (POI) domain or a fragment thereof; and(ii) at least one vesicle targeting domain, wherein the POI domain is inan extracellular position relative to a lipid membrane of theextracellular vesicle.

In some embodiments, the POI domain or a fragment thereof is aN-terminal domain of the fusion polypeptide. In some embodiments, thevesicle targeting domain or a fragment thereof is a C-terminal domain ofthe fusion polypeptide.

In another aspect, provided herein is an engineered extracellularvesicle comprising: at least one fusion polypeptide comprising: (i) atleast one protein of interest (POI) domain or a fragment thereof; and(ii) at least one vesicle targeting domain, wherein the POI domain is inan extracellular position relative to a lipid membrane of theextracellular vesicle, and wherein the vesicle targeting domain is atransmembrane domain relative to a lipid membrane of the extracellularvesicle.

In some embodiments, the POI domain or a fragment thereof is aC-terminal domain of the fusion polypeptide. In some embodiments, thevesicle targeting domain or a fragment thereof is a N-terminal domain ofthe fusion polypeptide. In some embodiments, the vesicle targetingdomain is in a luminal position relative to the lipid membrane of theextracellular vesicle.

In some embodiments, the linker is in an exterior position relative tothe lipid membrane of the extracellular vesicle. In some embodiments,the linker is a transmembrane linker. In some embodiments, the linker isin a luminal position relative to the lipid membrane of theextracellular vesicle.

The engineered extracellular vesicle compositions provided herein cancomprise one or more of the following fusion polypeptide sequences inTable 4.

TABLE 4 Full Length Constructs Nucleic Acid Sequence (SEQ ID NO:)Fusion Polypeptide Amino Acid Sequence (SEQ ID NO:)hCTLA4-Fc-GPI >Artificial sequence; hCTLA4-Fc-GPI, DNAATGGCTTGCCTTGGATTTCAGCGGCACAAGGCTCAGCTGAACCTGGCTACCAGGACCTGGCCCTGCACTCTCCTGTTTTTTCTTCTCTTCATCCCTGTCTTCTGCAAAGCAATGCACGTGGCCCAGCCTGCTGTGGTACTGGCCAGCAGCCGAGGCATCGCCAGCTTTGTGTGTGAGTATGCATCTCCAGGCAAAGCCACTGAGGTCCGGGTGACAGTGCTTCGGCAGGCTGACAGCCAGGTGACTGAAGTCTGTGCGGCAACCTACATGATGGGGAATGAGTTGACCTTCCTAGATGATTCCATCTGCACGGGCACCTCCAGTGGAAATCAAGTGAACCTCACTATCCAAGGACTGAGGGCCATGGACACGGGACTCTACATCTGCAAGGTGGAGCTCATGTACCCACCGCCATACTACCTGGGCATAGGCAACGGAACCCAGATTTATGTAATTGATCCAGAACCGTGCCCAGATTCTGACATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 223) > Artificial sequence; hCTLA4-Fc-GPI, Amino AcidMACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 224)hPDL1-GPI > Artificial sequence; hPDL1-GPI, DNAATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGG CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 225) >Amino Acid Sequence; hPDL1-GPI, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 226)hPDL1-C1C2 >Artificial Sequence; hPDL1-C1C2, DNAATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGGATCGATGTCGAGCCACTGGGCATGGAGAATGGGAACATTGCCAACTCACAGATCGCCGCCTCATCTGTGCGTGTGACCTTCTTGGGTTTGCAGCATTGGGTCCCGGAGCTGGCCCGCCTGAACCGCGCAGGCATGGTCAATGCCTGGACACCCAGCAGCAATGACGATAACCCCTGGATCCAGGTGAACCTGCTGCGGAGGATGTGGGTAACAGGTGTGGTGACGCAGGGTGCCAGCCGCTTGGCCAGTCATGAGTACCTGAAGGCCTTCAAGGTGGCCTACAGCCTTAATGGACACGAATTCGATTTCATCCATGATGTTAATAAAAAACACAAGGAGTTTGTGGGTAACTGGAACAAAAACGCGGTGCATGTCAACCTGTTTGAGACCCCTGTGGAGGCTCAGTACGTGAGATTGTACCCCACGAGCTGCCACACGGCCTGCACTCTGCGCTTTGAGCTACTGGGCTGTGAGCTGAACGGATGCGCCAATCCCCTGGGCCTGAAGAATAACAGCATCCCTGACAAGCAGATCACGGCCTCCAGCAGCTACAAGACCTGGGGCTTGCATCTCTTCAGCTGGAACCCCTCCTATGCACGGCTGGACAAGCAGGGCAACTTCAACGCCTGGGTTGCGGGGAGCTACGGTAACGATCAGTGGCTGCAGATCTTCCCTGGCAACTGGGACAACCACTCCCACAAGAAGAACTTGTTTGAGACGCCCATCCTGGCTCGCTATGTGCGCATCCTGCCTGTAGCCTGGCACAACCGCATCGCCCTGCGCCTGGAGCTGCTGGGCTGTTAG(SEQ ID NO: 227) >Artificial Sequence, hPDL1-C1C2, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPELPLAHPPNERIDVEPLGMENGNIANSQIAASSVRVTFLGLQHWVPELARLNRAGMVNAWTPSSNDDNPWIQVNLLRRMWVTGVVTQGASRLASHEYLKAFKVAYSLNGHEFDFIHDVNKKHKEFVGNWNKNAVHVNLFETPVEAQYVRLYPTSCHTACTLRFELLGCELNGCANPLGLKNNSIPDKQITASSSYKTWGLHLFSWNPSYARLDKQGNFNAWVAGSYGNDQWLQIFPGNWDNHSHKKNLFETPILARYVRILPVAWHNRIALRLELLGC (SEQ ID NO: 228)hPDL1-Fc-GPI >Artificial Sequence; hPDL1-Fc-GPI, DNAATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGGATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 229) > Artificial Sequence; hPDL1-Fc-GPI, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPELPLAHPPNERIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 230)hPDL2-C1C2 >Artificial Sequence; hPDL2-C1C2, DNAATGATCTTCCTCCTGCTAATGTTGAGCCTGGAATTGCAGCTTCACCAGATAGCAGCTTTATTCACAGTGACAGTCCCTAAGGAACTGTACATAATAGAGCATGGCAGCAATGTGACCCTGGAATGCAACTTTGACACTGGAAGTCATGTGAACCTTGGAGCAATAACAGCCAGTTTGCAAAAGGTGGAAAATGATACATCCCCACACCGTGAAAGAGCCACTTTGCTGGAGGAGCAGCTGCCCCTAGGGAAGGCCTCGTTCCACATACCTCAAGTCCAAGTGAGGGACGAAGGACAGTACCAATGCATAATCATCTATGGGGTCGCCTGGGACTACAAGTACCTGACTCTGAAAGTCAAAGCTTCCTACAGGAAAATAAACACTCACATCCTAAAGGTTCCAGAAACAGATGAGGTAGAGCTCACCTGCCAGGCTACAGGTTATCCTCTGGCAGAAGTATCCTGGCCAAACGTCAGCGTTCCTGCCAACACCAGCCACTCCAGGACCCCTGAAGGCCTCTACCAGGTCACCAGTGTTCTGCGCCTAAAGCCACCCCCTGGCAGAAACTTCAGCTGTGTGTTCTGGAATACTCACGTGAGGGAACTTACTTTGGCCAGCATTGACCTTCAAAGTCAGATGGAACCCAGGACCCATCCAACTATCGATGTCGAGCCACTGGGCATGGAGAATGGGAACATTGCCAACTCACAGATCGCCGCCTCATCTGTGCGTGTGACCTTCTTGGGTTTGCAGCATTGGGTCCCGGAGCTGGCCCGCCTGAACCGCGCAGGCATGGTCAATGCCTGGACACCCAGCAGCAATGACGATAACCCCTGGATCCAGGTGAACCTGCTGCGGAGGATGTGGGTAACAGGTGTGGTGACGCAGGGTGCCAGCCGCTTGGCCAGTCATGAGTACCTGAAGGCCTTCAAGGTGGCCTACAGCCTTAATGGACACGAATTCGATTTCATCCATGATGTTAATAAAAAACACAAGGAGTTTGTGGGTAACTGGAACAAAAACGCGGTGCATGTCAACCTGTTTGAGACCCCTGTGGAGGCTCAGTACGTGAGATTGTACCCCACGAGCTGCCACACGGCCTGCACTCTGCGCTTTGAGCTACTGGGCTGTGAGCTGAACGGATGCGCCAATCCCCTGGGCCTGAAGAATAACAGCATCCCTGACAAGCAGATCACGGCCTCCAGCAGCTACAAGACCTGGGGCTTGCATCTCTTCAGCTGGAACCCCTCCTATGCACGGCTGGACAAGCAGGGCAACTTCAACGCCTGGGTTGCGGGGAGCTACGGTAACGATCAGTGGCTGCAGATCTTCCCTGGCAACTGGGACAACCACTCCCACAAGAAGAACTTGTTTGAGACGCCCATCCTGGCTCGCTATGTGCGCATCCTGCCTGTAGCCTGGCACAACCGCATCGCCCTGCGCCTGGAGCTGCTGGGCTGTTAG(SEQ ID NO: 231) >Artificial Sequence; hPDL2-C1C2, Amino AcidMIFLLLMLSLELQLHQIAALFTVTVPKELYIIEHGSNVTLECNFDTGSHVNLGAITASLQKVENDTSPHRERATLLEEQLPLGKASFHIPQVQVRDEGQYQCIIIYGVAWDYKYLTLKVKASYRKINTHILKVPETDEVELTCQATGYPLAEVSWPNVSVPANTSHSRTPEGLYQVTSVLRLKPPPGRNFSCVFWNTHVRELTLASIDLQSQMEPRTHPTIDVEPLGMENGNIANSQIAASSVRVTFLGLQHWVPELARLNRAGMVNAWTPSSNDDNPWIQVNLLRRMWVTGVVTQGASRLASHEYLKAFKVAYSLNGHEFDFIHDVNKKHKEFVGNWNKNAVHVNLFETPVEAQYVRLYPTSCHTACTLRFELLGCELNGCANPLGLKNNSIPDKQITASSSYKTWGLHLFSWNPSYARLDKQGNFNAWVAGSYGNDQWLQIFPGNWDNHSHKKNLFETPILARYVRILPVAWHNRIALRLELLGC (SEQ ID NO: 232)hPDL2-Fc-GPI >Artificial Sequence; hPDL2-Fc-GPI, DNAATGATCTTCCTCCTGCTAATGTTGAGCCTGGAATTGCAGCTTCACCAGATAGCAGCTTTATTCACAGTGACAGTCCCTAAGGAACTGTACATAATAGAGCATGGCAGCAATGTGACCCTGGAATGCAACTTTGACACTGGAAGTCATGTGAACCTTGGAGCAATAACAGCCAGTTTGCAAAAGGTGGAAAATGATACATCCCCACACCGTGAAAGAGCCACTTTGCTGGAGGAGCAGCTGCCCCTAGGGAAGGCCTCGTTCCACATACCTCAAGTCCAAGTGAGGGACGAAGGACAGTACCAATGCATAATCATCTATGGGGTCGCCTGGGACTACAAGTACCTGACTCTGAAAGTCAAAGCTTCCTACAGGAAAATAAACACTCACATCCTAAAGGTTCCAGAAACAGATGAGGTAGAGCTCACCTGCCAGGCTACAGGTTATCCTCTGGCAGAAGTATCCTGGCCAAACGTCAGCGTTCCTGCCAACACCAGCCACTCCAGGACCCCTGAAGGCCTCTACCAGGTCACCAGTGTTCTGCGCCTAAAGCCACCCCCTGGCAGAAACTTCAGCTGTGTGTTCTGGAATACTCACGTGAGGGAACTTACTTTGGCCAGCATTGACCTTCAAAGTCAGATGGAACCCAGGACCCATCCAACTATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 233) >Artificial Sequence; hPDL2-Fc-GPI, Amino AcidMIFLLLMLSLELQLHQIAALFTVTVPKELYIIEHGSNVTLECNFDTGSHVNLGAITASLQKVENDTSPHRERATLLEEQLPLGKASFHIPQVQVRDEGQYQCIIIYGVAWDYKYLTLKVKASYRKINTHILKVPETDEVELTCQATGYPLAEVSWPNVSVPANTSHSRTPEGLYQVTSVLRLKPPPGRNFSCVFWNTHVRELTLASIDLQSQMEPRTHPTIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 234)4F2-h41BBL >Artificial Sequence; 4F2-41BBL, DNAATGAGCCAGGACACCGAGGTGGATATGAAGGAGGTGGAGCTGAATGAGTTAGAGCCCGAGAAGCAGCCGATGAACGCGGCGTCTGGGGCGGCCATGTCCCTGGCGGGAGCCGAGAAGAATGGTCTGGTGAAGATCAAGGTGGCGGAAGACGAGGCGGAGGCGGCAGCCGCGGCTAAGTTCACGGGCCTGTCCAAGGAGGAGCTGCTGAAGGTGGCAGGCAGCCCCGGCTGGGTACGCACCCGCTGGGCACTGCTGCTGCTCTTCTGGCTCGGCTGGCTCGGCATGCTTGCTGGTGCCGTGGTCATAATCGTG GCCTGCCCCTGGGCCGTGTCCGGGGCTCGCGCCTCGCCCGGCTCCGCGGCCAGCCCGAGACTCCGCGAGGGTCCCGAGCTTTCGCCCGACGATCCCGCCGGCCTCTTGGACCTGCGGCAGGGCATGTTTGCGCAGCTGGTGGCCCAAAATGTTCTGCTGATCGATGGGCCCCTGAGCTGGTACAGTGACCCAGGCCTGGCAGGCGTGTCCCTGACGGGGGGCCTGAGCTACAAAGAGGACACGAAGGAGCTGGTGGTGGCCAAGGCTGGAGTCTACTATGTCTTCTTTCAACTAGAGCTGCGGCGCGTGGTGGCCGGCGAGGGCTCAGGCTCCGTTTCACTTGCGCTGCACCTGCAGCCACTGCGCTCTGCTGCTGGGGCCGCCGCCCTGGCTTTGACCGTGGACCTGCCACCCGCCTCCTCCGAGGCTCGGAACTCGGCCTTCGGTTTCCAGGGCCGCTTGCTGCACCTGAGTGCCGGCCAGCGCCTGGGCGTCCATCTTCACACTGAGGCCAGGGCACGCCATGCCTGGCAGCTTACCCAGGGCGCCACAGTCTTGGGACTCTTCCGGGTGACCCCCGAAATCCCAGCCGGACTCCCTTCACCGAGGTCGGAATAA(SEQ ID NO: 235) >Artificial Sequence; 4F2-h41BBL, Amino AcidMSQDTEVDMKEVELNELEPEKQPMNAASGAAMSLAGAEKNGLVKIKVAEDEAEAAAAAKFTGLSKEELLKVAGSPGWVRTRWALLLLFWLGWLGMLAGAVVIIV ACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSPRSE (SEQ ID NO: 236)hPDL1-4Fc-GPI >Artificial Sequence; hPDL1-4Fc-GPI, DNAATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGG GAGTCCAAATATGGTCCCCCATGCCCATCATGCCCAGCACCTGAGTTCCTGGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGGGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGTAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGGACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCCGGGTAAA CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 237) >Artificial Sequence; hPDL1-4Fc-GPI, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVRVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEDNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHY TQKSLSLSPGKPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 238)hPDL1-GPI-P2A- >Artificial Sequence; hPDL1-GPI-P2A-hFGL1-GPI, DNAhFGL1-GPI ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGG CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTGGAAGCGGAGCTACTAACTTCAGCCTGCTGAAGCAGGCTGGCGACGTGGAGGAGAACCCTGGACCT ATGGCAAAGGTGTTCAGTTTCATCCTTGTTACCACCGCTCTGACAATGGGCAGGGAAATTTCGGCGCTCGAGGACTGTGCCCAGGAGCAGATGCGGCTCAGAGCCCAGGTGCGCCTGCTTGAGACCCGGGTCAAACAGCAACAGGTCAAGATCAAGCAGCTTTTGCAGGAGAATGAAGTCCAGTTCCTTGATAAAGGAGATGAGAATACTGTCATTGATCTTGGAAGCAAGAGGCAGTATGCAGATTGTTCAGAGATTTTCAATGATGGGTATAAGCTCAGTGGATTTTACAAAATCAAACCTCTCCAGAGCCCAGCAGAATTTTCTGTTTATTGTGACATGTCCGATGGAGGAGGATGGACTGTAATTCAGAGACGATCTGATGGCAGTGAAAACTTTAACAGAGGATGGAAAGACTATGAAAATGGCTTTGGAAATTTTGTCCAAAAACATGGTGAATATTGGCTGGGCAATAAAAATCTTCACTTCTTGACCACTCAAGAAGACTACACTTTAAAAATCGACCTTGCAGATTTTGAAAAAAATAGCCGTTATGCACAATATAAGAATTTCAAAGTTGGAGATGAAAAGAATTTCTACGAGTTGAATATTGGGGAATATTCTGGAACAGCTGGAGATTCCCTTGCGGGGAATTTTCATCCTGAGGTGCAGTGGTGGGCTAGTCACCAAAGAATGAAATTCAGCACGTGGGACAGAGATCATGACAACTATGAAGGGAACTGCGCAGAAGAAGATCAGTCTGGCTGGTGGTTTAACAGGTGTCACTCTGCAAACCTGAATGGTGTATACTACAGCGGCCCCTACACGGCTAAAACAGACAATGGGATTGTCTGGTACACCTGGCATGGGTGGTGGTATTCTCTGAAATCTGTGGTTATGAAAATTAGGCCAAATGATTTTATTCCAAATGTA ATTCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACT TAG(SEQ ID NO: 239) >Artificial Sequence; hPDL1-GPI-P2A-hFGL1-GPI, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLTGSGATNFSLL KQAGDVEENPGPMAKVFSFILVTTALTMGREISALEDCAQEQMRLRAQVRLLETRVKQQQVKIKQLLQENEVQFLDKGDENTVIDLGSKRQYADCSEIFNDGYKLSGFYKIKPLQSPAEFSVYCDMSDGGGWTVIQRRSDGSENFNRGWKDYENGFGNFVQKHGEYWLGNKNLHFLTTQEDYTLKIDLADFEKNSRYAQYKNFKVGDEKNFYELNIGEYSGTAGDSLAGNFHPEVQWWASHQRMKFSTWDRDHDNYEGNCAEEDQSGWWFNRCHSANLNGVYYSGPYTAKTDNGIVWYTWHGWWYSLKSVVMKIRPNDFIPNVI PNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 240)Myr-mScarlet >Artificial Sequence; Myr-mScarlet, DNAATGGGTTGCTGTTTCTCCAAGACC GGCTCGAGCGGCGTGAGCAAGGGCGAGGCAGTGATCAAGGAGTTCATGCGGTTCAAGGTGCACATGGAGGGCTCCATGAACGGCCACGAGTTCGAGATCGAGGGCGAGGGCGAGGGCCGCCCCTACGAGGGCACCCAGACCGCCAAGCTGAAGGTGACCAAGGGTGGCCCCCTGCCCTTCTCCTGGGACATCCTGTCCCCTCAGTTCATGTACGGCTCCAGGGCCTTCACCAAGCACCCCGCCGACATCCCCGACTACTATAAGCAGTCCTTCCCCGAGGGCTTCAAGTGGGAGCGCGTGATGAACTTCGAGGACGGCGGCGCCGTGACCGTGACCCAGGACACCTCCCTGGAGGACGGCACCCTGATCTACAAGGTGAAGCTCCGCGGCACCAACTTCCCTCCTGACGGCCCCGTAATGCAGAAGAAGACAATGGGCTGGGAAGCGTCCACCGAGCGGTTGTACCCCGAGGACGGCGTGCTGAAGGGCGACATTAAGATGGCCCTGCGCCTGAAGGACGGCGGCCGCTACCTGGCGGACTTCAAGACCACCTACAAGGCCAAGAAGCCCGTGCAGATGCCCGGCGCCTACAACGTCGACCGCAAGTTGGACATCACCTCCCACAACGAGGACTACACCGTGGTGGAACAGTACGAACGCTCCGAGGGCCGCCACTCCACCGGCGGCATGGACGAGCTGTACAAG(SEQ ID NO: 241) >Artificial Sequence; Myr-mScarlet, Amino Acid MGCCFSKTGSSGVSKGEAVIKEFMRFKVHMEGSMNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFSWDILSPQFMYGSRAFTKHPADIPDYYKQSFPEGFKWERVMNFEDGGAVTVTQDTSLEDGTLIYKVKLRGTNFPPDGPVMQKKTMGWEASTERLYPEDGVLKGDIKMALRLKDGGRYLADFKTTYKAKKPVQMPGAYNVDRKLDITSHNEDYTVVEQYERSEGRHSTGGMDELYK (SEQ ID NO: 242)Myr-NanoLuc > Artificial Sequence; Myr-NanoLuc, DNA LuciferaseATGGGTTGCTGTTTCTCCAAGACC GGCTCGAGCGGCGTCTTCACACTCGAAGATTTCGTTGGGGACTGGCGACAGACAGCCGGCTACAACCTGGACCAAGTCCTTGAACAGGGAGGTGTGTCCAGTTTGTTTCAGAATCTCGGGGTGTCCGTAACTCCGATCCAAAGGATTGTCCTGAGCGGTGAAAATGGGCTGAAGATCGACATCCATGTCATCATCCCGTATGAAGGTCTGAGCGGCGACCAAATGGGCCAGATCGAAAAAATTTTTAAGGTGGTGTACCCTGTGGATGATCATCACTTTAAGGTGATCCTGCACTATGGCACACTGGTAATCGACGGGGTTACGCCGAACATGATCGACTATTTCGGACGGCCGTATGAAGGCATCGCCGTGTTCGACGGCAAAAAGATCACTGTAACAGGGACCCTGTGGAACGGCAACAAAATTATCGACGAGCGCCTGATCAACCCCGACGGCTCCCTGCTGTTCCGAGTAACCATCAACGGAGTGACCGGCTGGCGGCTGTGCGAACGCATTCTGGCGTAA(SEQ ID NO: 243) >Artificial Sequence; Myr-NanoLuc, Amino Acid MGCCFSKTGSSGVFTLEDFVGDWRQTAGYNLDQVLEQGGVSSLFQNLGVSVTPIQRIVLSGENGLKIDIHVIIPYEGLSGDQMGQIEKIFKVVYPVDDHHFKVILHYGTLVIDGVTPNMIDYFGRPYEGIAVFDGKKITVTGTLWNGNKIIDERLINPDGSLLFRVTINGV TGWRLCERILA(SEQ ID NO: 244) hSecPDL1-GPI >Artificial Sequence; hSecPDL1-GPI, DNAATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGGTAATATTCTGAATGTGTCCATTAAAATATGTCTAACACTGTCCCCTAGCACC CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 245) >Artificial Sequence; hSecPDL1-GPI, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPGNILNVSIKICLTLSPST PNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 246)Tfr2-h41BBL >Artificial Sequence; Tfr2-h41BBL, DNAATGGAGCGGCTTTGGGGTCTATTCCAGAGAGCGCAACAACTGTCCCCAAGATCCTCTCAGACCGTCTACCAGCGTGTGGAAGGCCCCCGGAAAGGGCACCTGGAGGAGGAAGAGGAAGACGGGGAGGAGGGGGCGGAGACATTGGCCCACTTCTGCCCCATGGAGCTGAGGGGCCCTGAGCCCCTGGGCTCTAGACCCAGGCAGCCAAACCTCATTCCCTGGGCGGCAGCAGGACGGAGGGCTGCCCCCTACCTGGTCCTGACGGCCCTGCTGATCTTCACTGGGGCCTTCCTACTGGGCTACGTCGCCTTCCGAGGGTCC

(SEQ ID NO: 247) >Artificial Sequence; Tfr2-h41BBL, Amino AcidMERLWGLFQRAQQLSPRSSQTVYQRVEGPRKGHLEEEEEDGEEGAETLAHFCPMELRGPEPLGSRPRQPNLIPWAAAGRRAAPYLVLTALLIFTGAFLLGYVAFRGS ACPWAVSGARASPGSAASPRLRGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSPRSE (SEQ ID NO: 248)CD9tm3-h41BBL >Artificial Sequence; CD9tm3-h41BBL, DNAATGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGCATGCTGGGACTGTTCTTCGGCTTCCTCTTGGTGATATTCGCCATTGAAATAGCTGCGGCCATCTGGGGATATTCCCAC AAGGATGAGGCCTGCCCCTGGGCCGTGTCCGGGGCTCGCGCCTCGCCCGGCTCCGCGGCCAGCCCGAGACTCCGCGAGGGTCCCGAGCTTTCGCCCGACGATCCCGCCGGCCTCTTGGACCTGCGGCAGGGCATGTTTGCGCAGCTGGTGGCCCAAAATGTTCTGCTGATCGATGGGCCCCTGAGCTGGTACAGTGACCCAGGCCTGGCAGGCGTGTCCCTGACGGGGGGCCTGAGCTACAAAGAGGACACGAAGGAGCTGGTGGTGGCCAAGGCTGGAGTCTACTATGTCTTCTTTCAACTAGAGCTGCGGCGCGTGGTGGCCGGCGAGGGCTCAGGCTCCGTTTCACTTGCGCTGCACCTGCAGCCACTGCGCTCTGCTGCTGGGGCCGCCGCCCTGGCTTTGACCGTGGACCTGCCACCCGCCTCCTCCGAGGCTCGGAACTCGGCCTTCGGTTTCCAGGGCCGCTTGCTGCACCTGAGTGCCGGCCAGCGCCTGGGCGTCCATCTTCACACTGAGGCCAGGGCACGCCATGCCTGGCAGCTTACCCAGGGCGCCACAGTCTTGGGACTCTTCCGGGTGACCCCCGAAATCCCAGCCGGACTCCCTTCACCGAGGTCGGAATAA(SEQ ID NO: 249) >Artificial Sequence; CD9tm3-h41BBL, Amino AcidMGCCGAVQESQCMLGLFFGFLLVIFAIEIAAAIWGYSHKDE ACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSPRSE (SEQ ID NO: 250)Myr/Palm-4F2- >Artificial Sequence; Myr/Palm-4F2-h41BBL, DNA h41BBLATGGGTTGCTGTTTCTCCAAGACC GGCTCGAGOGGCAGCCAGGACACCGAGGTGGATATGAAGGAGGTGGAGCTGAATGAGTTAGAGCCCGAGAAGCAGCCGATGAACGCGGCGTCTGGGGCGGCCATGTCCCTGGCGGGAGCCGAGAAGAATGGTCTGGTGAAGATCAAGGTGGCGGAAGACGAGGCGGAGGCGGCAGCCGCGGCTAAGTTCACGGGCCTGTCCAAGGAGGAGCTGCTGAAGGTGGCAGGCAGCCCCGGCTGGGTACGCACCCGCTGGGCACTGCTGCTGCTCTTCTGGCTCGGCTGGCTCGGCATGCTTGCTGGTGCCGTGGTCATAATC GTGGCCTGCCCCTGGGCCGTGTCCGGGGCTCGCGCCTCGCCCGGCTCCGCGGCCAGCCCGAGACTCCGCGAGGGTCCCGAGCTTTCGCCCGACGATCCCGCCGGCCTCTTGGACCTGCGGCAGGGCATGTTTGCGCAGCTGGTGGCCCAAAATGTTCTGCTGATCGATGGGCCCCTGAGCTGGTACAGTGACCCAGGCCTGGCAGGCGTGTCCCTGACGGGGGGCCTGAGCTACAAAGAGGACACGAAGGAGCTGGTGGTGGCCAAGGCTGGAGTCTACTATGTCTTCTTTCAACTAGAGCTGCGGCGCGTGGTGGCCGGCGAGGGCTCAGGCTCCGTTTCACTTGCGCTGCACCTGCAGCCACTGCGCTCTGCTGCTGGGGCCGCCGCCCTGGCTTTGACCGTGGACCTGCCACCCGCCTCCTCCGAGGCTCGGAACTCGGCCTTCGGTTTCCAGGGCCGCTTGCTGCACCTGAGTGCCGGCCAGCGCCTGGGCGTCCATCTTCACACTGAGGCCAGGGCACGCCATGCCTGGCAGCTTACCCAGGGCGCCACAGTCTTGGGACTCTTCCGGGTGACCCCCGAAATCCCAGCCGGACTCCCTTCACCGAGGTCGGAATAA(SEQ ID NO: 251) >Artificial Sequence; Myr/Palm-4F2-h41BBL, Amino AcidMGCCFSKTGSSGSQDTEVDMKEVELNELEPEKQPMNAASGAAMSLAGAEKNGLVKIKVAEDEAEAAAAAKFTGLSKEELLKVAGSPGWVRTRWALLLLFWLGWLGMLAGAVVII VACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSPRSE (SEQ ID NO: 252)Myr/Palm-Link- >Artificial Sequence; Myr/Palm-Link-41BBL, DNA41BBL (41BBL ATGGGTTGCTGTTTCTCCAAGACC GGCTCGAGCGGCTGGGCCCTGGTCGCGGGGCTGtransmembrane CTGCTGCTGCTGCTGCTCGCTGCCGCCTGCGCCGTCTTCCTCGCCTGCCCCTGGGCCdomain GTGTCCGGGGCTCGCGCCTCGCCCGGCTCCGCGGCCAGCCCGAGACTCCGCGAGGGTincluded) CCCGAGCTTTCGCCCGACGATCCCGCCGGCCTCTTGGACCTGCGGCAGGGCATGTTTGCGCAGCTGGTGGCCCAAAATGTTCTGCTGATCGATGGGCCCCTGAGCTGGTACAGTGACCCAGGCCTGGCAGGCGTGTCCCTGACGGGGGGCCTGAGCTACAAAGAGGACACGAAGGAGCTGGTGGTGGCCAAGGCTGGAGTCTACTATGTCTTCTTTCAACTAGAGCTGCGGCGCGTGGTGGCCGGCGAGGGCTCAGGCTCCGTTTCACTTGCGCTGCACCTGCAGCCACTGCGCTCTGCTGCTGGGGCCGCCGCCCTGGCTTTGACCGTGGACCTGCCACCCGCCTCCTCCGAGGCTCGGAACTCGGCCTTCGGTTTCCAGGGCCGCTTGCTGCACCTGAGTGCCGGCCAGCGCCTGGGCGTCCATCTTCACACTGAGGCCAGGGCACGCCATGCCTGGCAGCTTACCCAGGGCGCCACAGTCTTGGGACTCTTCCGGGTGACCCCCGAAATCCCAGCCGGACTCCCTTCACCGAGGTCGGAATAA(SEQ ID NO: 253) >Artificial Sequence; Myr/Palm-Link-41BBL, Amino AcidMGCCFSKT GSSGWALVAGLLLLLLLAAACAVFLACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEI PAGLPSPRSE(SEQ ID NO: 254)hPDL1-Link-GPI >Artificial Sequence; hPDL1-Link-GPI, DNAATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAANGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTG GGCTCGAGCGGCCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 255) >Artificial Sequence; hPDL1-Link-GPI, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAEL GSSGPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 256)hSecPDL1- >Artificial Sequence; hSecPDL1-CD9tm2, DNA CD9tm2ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGGTAATATTCTGAATGTGTCCATTAAAATATGTCTAACACTGTCCCCTAGCACC TTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGCTAG(SEQ ID NO: 257) >Artificial Sequence; hSecPDL1-CD9tm2, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPGNILNVSIKICLTLSPST FYTGVYILIGAGALMMLVGFLGCCGAVQESQC (SEQ ID NO: 258)hSecPDL1- >Artificial Sequence; hSecPDL1-CD9tm2-KRAS, DNA CD9tm2-ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT modified KRASACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGGTAATATTCTGAATGTGTCCATTAAAATATGTCTAACACTGTCCCCTAGCACC TTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGC AAAAAGAAGAAAAAGAAGTCAAAGACAAAGTGTGTAATTATGTAA(SEQ ID NO: 259) >Artificial Sequence; hSecPDL1-CD9tm2-KRAS, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPGNILNVSIKICLTLSPST FYTGVYILIGAGALMMLVGFLGCCGAVQESQC KKKKKKSK TKCVIM(SEQ ID NO: 260) hSecPDL1- >Artificial Sequence; hSecPDL1-CD9tm4, DNACD9tm4 ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGGTAATATTCTGAATGTGTCCATTAAAATATGTCTAACACTGTCCCCTAGCACC ATCGGCGCAGTGGGCATCGGCATTGCCGTGGTCATGATATTTGGCATGATCTTCAGTATGATCTTGTGCTGTGCTATCCGCAGGAACCGCGAGATGGTCTAG(SEQ ID NO: 261) >Artificial Sequence; hSecPDL1-CD9tm4, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTIAINTTTNEIFYCTFRRLDPEENHTAELVIPGNILNVSIKICLTLSPST IGAVGIGIAVVMIFGMIFSMILCCAIRRNREMV (SEQ ID NO: 262)hSecPDL1-CD81 >Artificial Sequence; hSecPDL1-CD81, DNAATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGGTAATATTCTGAATGTGTCCATTAAAATATGTCTAACACTGTCCCCTAGCACC CTGTACCTCATCGGCATTGCTGCCATCGTGGTCGCTGTGATCATGATCTTCGAGATGATCCTGAGCATGGTGCTGTGCTGTGGCATCCGGAACAGCTCCGTGTACTGA(SEQ ID NO: 263) >Artificial Sequence; hSecPDL1-CD81, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPGNILNVSIKICLTLSPST LYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY (SEQ ID NO: 264)hCD200-Fc-GPI >Artificial Sequence; hCD200-Fc-GPI, DNAATGGAGAGGCTGGTGATCAGGATGCCCTTCTCTCATCTGTCTACCTACAGCCTGGTTTGGGTCATGGCAGCAGTGGTGCTGTGCACAGCACAAGTGCAAGTGGTGACCCAGGATGAAAGAGAGCAGCTGTACACACCTGCTTCCTTAAAATGCTCTCTGCAAAATGCCCAGGAAGCCCTCATTGTGACATGGCAGAAAAAGAAAGCTGTAAGCCCAGAAAACATGGTCACCTTCAGCGAGAACCATGGGGTGGTGATCCAGCCTGCCTATAAGGACAAGATAAACATTACCCAGCTGGGACTCCAAAACTCAACCATCACCTTCTGGAATATCACCCTGGAGGATGAAGGGTGTTACATGTGTCTCTTCAATACCTTTGGTTTTGGGAAGATCTCAGGAACGGCCTGCCTCACCGTCTATGTACAGCCCATAGTATCCCTTCACTACAAATTCTCTGAAGACCACCTAAATATCACTTGCTCTGCCACTGCCCGCCCAGCCCCCATGGTCTTCTGGAAGGTCCCTCGGTCAGGGATTGAAAATAGTACAGTGACTCTGTCTCACCCAAATGGGACCACGTCTGTTACCAGCATCCTCCATATCAAAGACCCTAAGAATCAGGTGGGGAAGGAGGTGATCTGCCAGGTGCTGCACCTGGGGACTGTGACCGACTTTAAGCAAACCGTCAACAAAGGCATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 265) >Artificial Sequence; hCD200-Fc-GPI, Amino AcidMERLVIRMPFSHLSTYSLVWVMAAVVLCTAQVQVVTQDEREQLYTPASLKCSLQNAQEALIVTWQKKKAVSPENMVTFSENHGVVIQPAYKDKINITQLGLQNSTITFWNITLEDEGCYMCLFNTFGFGKISGTACLTVYVQPIVSLHYKFSEDHLNITCSATARPAPMVFWKVPRSGIENSTVTLSHPNGTTSVTSILHIKDPKNQVGKEVICQVLHLGTVTDFKQTVNKGIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 266)hFGL1-GPI >Artificial Sequence; hFGL1-GPI, DNAATGGCAAAGGTGTTCAGTTTCATCCTTGTTACCACCGCTCTGACAATGGGCAGGGAAATTTCGGCGCTCGAGGACTGTGCCCAGGAGCAGATGCGGCTCAGAGCCCAGGTGCGCCTGCTTGAGACCCGGGTCAAACAGCAACAGGTCAAGATCAAGCAGCTTTTGCAGGAGAATGAAGTCCAGTTCCTTGATAAAGGAGATGAGAATACTGTCATTGATCTTGGAAGCAAGAGGCAGTATGCAGATTGTTCAGAGATTTTCAATGATGGGTATAAGCTCAGTGGATTTTACAAAATCAAACCTCTCCAGAGCCCAGCAGAATTTTCTGTTTATTGTGACATGTCCGATGGAGGAGGATGGACTGTAATTCAGAGACGATCTGATGGCAGTGAAAACTTTAACAGAGGATGGAAAGACTATGAAAATGGCTTTGGAAATTTTGTCCAAAAACATGGTGAATATTGGCTGGGCAATAAAAATCTTCACTTCTTGACCACTCAAGAAGACTACACTTTAAAAATCGACCTTGCAGATTTTGAAAAAAATAGCCGTTATGCACAATATAAGAATTTCAAAGTTGGAGATGAAAAGAATTTCTACGAGTTGAATATTGGGGAATATTCTGGAACAGCTGGAGATTCCCTTGCGGGGAATTTTCATCCTGAGGTGCAGTGGTGGGCTAGTCACCAAAGAATGAAATTCAGCACGTGGGACAGAGATCATGACAACTATGAAGGGAACTGCGCAGAAGAAGATCAGTCTGGCTGGTGGTTTAACAGGTGTCACTCTGCAAACCTGAATGGTGTATACTACAGCGGCCCCTACACGGCTAAAACAGACAATGGGATTGTCTGGTACACCTGGCATGGGTGGTGGTATTCTCTGAAATCTGTGGTTATGAAAATTAGGCCAAATGATTTTATTCCAAATGTAATT CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 267) >Artificial Sequence; hFGL1-GPI, Amino AcidMAKVFSFILVTTALTMGREISALEDCAQEQMRLRAQVRLLETRVKQQQVKIKQLLQENEVQFLDKGDENTVIDLGSKRQYADCSEIFNDGYKLSGFYKIKPLQSPAEFSVYCDMSDGGGWTVIQRRSDGSENFNRGWKDYENGFGNFVQKHGEYWLGNKNLHFLTTQEDYTLKIDLADFEKNSRYAQYKNFKVGDEKNFYELNIGEYSGTAGDSLAGNFHPEVQWWASHQRMKFSTWDRDHDNYEGNCAEEDQSGWWFNRCHSANLNGVYYSGPYTAKTDNGIVWYTWHGWWYSLKSVVMKIRPNDFIPNVI PNKGSGTTSGTTRLLSGHTCFTLTGLLGTL VTMGLLT(SEQ ID NO: 268) hGa19-Fc-GPI >Artificial Sequence; hGal9-Fc-GPI, DNAATGGCCTTCAGCGGTTCCCAGGCTCCCTACCTGAGTCCAGCTGTCCCCTTTTCTGGGACTATTCAAGGAGGTCTCCAGGACGGACTTCAGATCACTGTCAATGGGACCGTTCTCAGCTCCAGTGGAACCAGGTTTGCTGTGAACTTTCAGACTGGCTTCAGTGGAAATGACATTGCCTTCCACTTCAACCCTCGGTTTGAAGATGGAGGGTACGTGGTGTGCAACACGAGGCAGAACGGAAGCTGGGGGCCCGAGGAGAGGAAGACACACATGCCTTTCCAGAAGGGGATGCCCTTTGACCTCTGCTTCCTGGTGCAGAGCTCAGATTTCAAGGTGATGGTGAACGGGATCCTCTTCGTGCAGTACTTCCACCGCGTGCCCTTCCACCGTGTGGACACCATCTCCGTCAATGGCTCTGTGCAGCTGTCCTACATCAGCTTCCAGAACCCCCGCACAGTCCCTGTTCAGCCTGCCTTCTCCACGGTGCCGTTCTCCCAGCCTGTCTGTTTCCCACCCAGGCCCAGGGGGCGCAGACAAAAACCTCCCGGCGTGTGGCCTGCCAACCCGGCTCCCATTACCCAGACAGTCATCCACACAGTGCAGAGCGCCCCTGGACAGATGTTCTCTACTCCCGCCATCCCACCTATGATGTACCCCCACCCCGCCTATCCGATGCCTTTCATCACCACCATTCTGGGAGGGCTGTACCCATCCAAGTCCATCCTCCTGTCAGGCACTGTCCTGCCCAGTGCTCAGAGGTTCCACATCAACCTGTGCTCTGGGAACCACATCGCCTTCCACCTGAACCCCCGTTTTGATGAGAATGCTGTGGTCCGCAACACCCAGATCGACAACTCCTGGGGGTCTGAGGAGCGAAGTCTGCCCCGAAAAATGCCCTTCGTCCGTGGCCAGAGCTTCTCAGTGTGGATCTTGTGTGAAGCTCACTGCCTCAAGGTGGCCGTGGATGGTCAGCACCTGTTTGAATACTACCATCGCCTGAGGAACCTGCCCACCATCAACAGACTGGAAGTGGGGGGCGACATCCAGCTGACCCATGTGCAGACAATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 269) >Artificial Sequence; hGal9-Fc-GPI, Amino AcidMAFSGSQAPYLSPAVPFSGTIQGGLQDGLQITVNGTVLSSSGTRFAVNFQTGFSGNDIAFHFNPRFEDGGYVVCNTRQNGSWGPEERKTHMPFQKGMPFDLCFLVQSSDFKVMVNGILFVQYFHRVPFHRVDTISVNGSVQLSYISFQNPRTVPVQPAFSTVPFSQPVCFPPRPRGRRQKPPGVWPANPAPITQTVIHTVQSAPGQMFSTPAIPPMMYPHPAYPMPFITTILGGLYPSKSILLSGTVLPSAQRFHINLCSGNHIAFHLNPRFDENAVVRNTQIDNSWGSEERSLPRKMPFVRGQSFSVWILCEAHCLKVAVDGQHLFEYYHRLRNLPTINRLEVGGDIQLTHVQTIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 270)hCD200-GPI >Artificial Sequence; hCD200-GPI, DNAATGGAGAGGCTGGTGATCAGGATGCCCTTCTCTCATCTGTCTACCTACAGCCTGGTTTGGGTCATGGCAGCAGTGGTGCTGTGCACAGCACAAGTGCAAGTGGTGACCCAGGATGAAAGAGAGCAGCTGTACACACCTGCTTCCTTAAAATGCTCTCTGCAAAATGCCCAGGAAGCCCTCATTGTGACATGGCAGAAAAAGAAAGCTGTAAGCCCAGAAAACATGGTCACCTTCAGCGAGAACCATGGGGTGGTGATCCAGCCTGCCTATAAGGACAAGATAAACATTACCCAGCTGGGACTCCAAAACTCAACCATCACCTTCTGGAATATCACCCTGGAGGATGAAGGGTGTTACATGTGTCTCTTCAATACCTTTGGTTTTGGGAAGATCTCAGGAACGGCCTGCCTCACCGTCTATGTACAGCCCATAGTATCCCTTCACTACAAATTCTCTGAAGACCACCTAAATATCACTTGCTCTGCCACTGCCCGCCCAGCCCCCATGGTCTTCTGGAAGGTCCCTCGGTCAGGGATTGAAAATAGTACAGTGACTCTGTCTCACCCAAATGGGACCACGTCTGTTACCAGCATCCTCCATATCAAAGACCCTAAGAATCAGGTGGGGAAGGAGGTGATCTGCCAGGTGCTGCACCTGGGGACTGTGACCGACTTTAAGCAAACC GTCAACAAAGGCCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGC TTGCTGACTTAG(SEQ ID NO: 271) >Artificial Sequence; hCD200-GPI, Amino AcidMERLVIRMPFSHLSTYSLVWVMAAVVLCTAQVQVVTQDEREQLYTPASLKCSLQNAQEALIVTWQKKKAVSPENMVTFSENHGVVIQPAYKDKINITQLGLQNSTITFWNITLEDEGCYMCLFNTFGFGKISGTACLTVYVQPIVSLHYKFSEDHLNITCSATARPAPMVFWKVPRSGIENSTVTLSHPNGTTSVTSILHIKDPKNQVGKEVICQVLHLGTVTDFKQT VNKGPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 272)hGal9-GPI >Artificial Sequence; hGa19-GPI, DNAATGGCCTTCAGCGGTTCCCAGGCTCCCTACCTGAGTCCAGCTGTCCCCTTTTCTGGGACTATTCAAGGAGGTCTCCAGGACGGACTTCAGATCACTGTCAATGGGACCGTTCTCAGCTCCAGTGGAACCAGGTTTGCTGTGAACTTTCAGACTGGCTTCAGTGGAAATGACATTGCCTTCCACTTCAACCCTCGGTTTGAAGATGGAGGGTACGTGGTGTGCAACACGAGGCAGAACGGAAGCTGGGGGCCCGAGGAGAGGAAGACACACATGCCTTTCCAGAAGGGGATGCCCTTTGACCTCTGCTTCCTGGTGCAGAGCTCAGATTTCAAGGTGATGGTGAACGGGATCCTCTTCGTGCAGTACTTCCACCGCGTGCCCTTCCACCGTGTGGACACCATCTCCGTCAATGGCTCTGTGCAGCTGTCCTACATCAGCTTCCAGAACCCCCGCACAGTCCCTGTTCAGCCTGCCTTCTCCACGGTGCCGTTCTCCCAGCCTGTCTGTTTCCCACCCAGGCCCAGGGGGCGCAGACAAAAACCTCCCGGCGTGTGGCCTGCCAACCCGGCTCCCATTACCCAGACAGTCATCCACACAGTGCAGAGCGCCCCTGGACAGATGTTCTCTACTCCCGCCATCCCACCTATGATGTACCCCCACCCCGCCTATCCGATGCCTTTCATCACCACCATTCTGGGAGGGCTGTACCCATCCAAGTCCATCCTCCTGTCAGGCACTGTCCTGCCCAGTGCTCAGAGGTTCCACATCAACCTGTGCTCTGGGAACCACATCGCCTTCCACCTGAACCCCCGTTTTGATGAGAATGCTGTGGTCCGCAACACCCAGATCGACAACTCCTGGGGGTCTGAGGAGCGAAGTCTGCCCCGAAAAATGCCCTTCGTCCGTGGCCAGAGCTTCTCAGTGTGGATCTTGTGTGAAGCTCACTGCCTCAAGGTGGCCGTGGATGGTCAGCACCTGTTTGAATACTACCATCGCCTGAGGAACCTGCCCACCATCAACAGACTGGAAGTGGGGGGCGACATCCAGCTGACCCATGTGCAGACA CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 273) >Artificial Sequence; hGal9-GPI, Amino AcidMAFSGSQAPYLSPAVPFSGTIQGGLQDGLQITVNGTVLSSSGTRFAVNFQTGFSGNDIAFHFNPRFEDGGYVVCNTRQNGSWGPEERKTHMPFQKGMPFDLCFLVQSSDFKVMVNGILFVQYFHRVPFHRVDTISVNGSVQLSYISFQNPRTVPVQPAFSTVPFSQPVCFPPRPRGRRQKPPGVWPANPAPITQTVIHTVQSAPGQMPSTPAIPPMMYPHPAYPMPFITTILGGLYPSKSILLSGTVLPSAQRFHINLCSGNHIAFHLNPRFDENAVVRNTQIDNSWGSEERSLPRKMPFVRGQSFSVWILCEAHCLKVAVDGQHLFEYYHRLRNLPTINRL EVGGDIQLTHVQTPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 274) hHVEM-GPI>Artificial Sequence; hHVEM-GPI, DNA

CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 275) >Artificial Sequence; hHVEM-GPI, Amino AcidMEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKEDEYPVGSECCPKCSPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCDPAMGLRASRNCSRTENAVCGCSPGHFCIVQDGDHCAACRAYATSSPGQRVQKGGTESQDTLCQNCPPGTFSPNGTLEECQHQTKCSWLVTKAGAGTSSSHWV PNKGSGTTSGTTRLLSGHTCFTLTGL LGTLVTMGLLT(SEQ ID NO: 276) hPDL2-GPI >Artificial Sequence; hPDL2-GPI, DNAATGATCTTCCTCCTGCTAATGTTGAGCCTGGAATTGCAGCTTCACCAGATAGCAGCTTTATTCACAGTGACAGTCCCTAAGGAACTGTACATAATAGAGCATGGCAGCAATGTGACCCTGGAATGCAACTTTGACACTGGAAGTCATGTGAACCTTGGAGCAATAACAGCCAGTTTGCAAAAGGTGGAAAATGATACATCCCCACACCGTGAAAGAGCCACTTTGCTGGAGGAGCAGCTGCCCCTAGGGAAGGCCTCGTTCCACATACCTCAAGTCCAAGTGAGGGACGAAGGACAGTACCAATGCATAATCATCTATGGGGTCGCCTGGGACTACAAGTACCTGACTCTGAAAGTCAAAGCTTCCTACAGGAAAATAAACACTCACATCCTAAAGGTTCCAGAAACAGATGAGGTAGAGCTCACCTGCCAGGCTACAGGTTATCCTCTGGCAGAAGTATCCTGGCCAAACGTCAGCGTTCCTGCCAACACCAGCCACTCCAGGACCCCTGAAGGCCTCTACCAGGTCACCAGTGTTCTGCGCCTAAAGCCACCCCCTGGCAGAAACTTCAGCTGTGTGTTCTGGAATACTCACGTGAGGGAACTTACTTTGGCCAGCATTGACCTTCAAAGTCAGATGGAACCCAGGACCCATCCAACT CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 277) >Artificial Sequence; hPDL2-GPI, Amino AcidMIFLLLMLSLELQLHQIAALFTVTVPKELYIIEHGSNVTLECNFDTGSHVNLGAITASLQKVENDTSPHRERATLLEEQLPLGKASFHIPQVQVRDEGQYQCIIIYGVAWDYKYLTLKVKASYRKINTHILKVPETDEVELTCQATGYPLAEVSWPNVSVPANTSHSRTPEGLYQVTSVLRLKPPPGRNFSCVFWNTHVRELTLASIDLQSQMEPRTHPT PNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 278)hTSG6-GPI >Artificial Sequence; hTSG6-GPI, DNAATGATCATCTTAATTTACTTATTTCTCTTGCTATGGGAAGACACTCAAGGATGGGGATTCAAGGATGGAATTTTTCATAACTCCATATGGCTTGAACGAGCAGCCGGTGTGTACCACAGAGAAGCACGGTCTGGCAAATACAAGCTCACCTACGCAGAAGCTAAGGCGGTGTGTGAATTTGAAGGCGGCCATCTCGCAACTTACAAGCAGCTAGAGGCAGCCAGAAAAATTGGATTTCATGTCTGTGCTGCTGGATGGATGGCTAAGGGCAGAGTTGGATACCCCATTGTGAAGCCAGGGCCCAACTGTGGATTTGGAAAAACTGGCATTATTGATTATGGAATCCGTCTCAATAGGAGTGAAAGATGGGATGCCTATTGCTACAACCCACACGCAAAGGAGTGTGGTGGCGTCTTTACAGATCCAAAGCAAATTTTTAAATCTCCAGGCTTCCCAAATGAGTACGAAGATAACCAAATCTGCTACTGGCACATTAGACTCAAGTATGGTCAGCGTATTCACCTGAGTTTTTTAGATTTTGACCTTGAAGATGACCCAGGTTGCTTGGCTGATTATGTTGAAATATATGACAGTTACGATGATGTCCATGGCTTTGTGGGAAGATACTGTGGAGATGAGCTTCCAGATGACATCATCAGTACAGGAAATGTCATGACCTTGAAGTTTCTAAGTGATGCTTCAGTGACAGCTGGAGGTTTCCAAATCAAATATGTTGCAATGGATCCTGTATCCAAATCCAGTCAAGGAAAAAATACAAGTACTACTTCTACTGGAAATAAAAACTTTTTAGCTGGAAGATTTAGCCACTTAATCGATCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 279) >Artificial Sequence; hTSG6-GPI, Amino AcidMIILIYLFLLLWEDTQGWGFKDGIFHNSIWLERAAGVYHREARSGKYKLTYAEAKAVCEFEGGHLATYKQLEAARKIGFHVCAAGWMAKGRVGYPIVKPGPNCGFGKTGIIDYGIRLNRSERWDAYCYNPHAKECGGVFTDPKQIFKSPGFPNEYEDNQICYWHIRLKYGQRIHLSFLDFDLEDDPGCLADYVEIYDSYDDVHGFVGRYCGDELPDDIISTGNVMTLKFLSDASVTAGGFQIKYVAMDPVSKSSQGKNTSTTSTGNKNFLAGRFSHLIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 280)hHVEM-Fc-GPI >Artificial Sequence; hHVEM-Fc-GPI, DNAATGGAGCCTCCTGGAGACTGGGGGCCTCCTCCCTGGAGATCCACCCCCAAAACCGACGTCTTGAGGCTGGTGCTGTATCTCACCTTCCTGGGAGCCCCCTGCTACGCCCCAGCTCTGCCGTCCTGCAAGGAGGACGAGTACCCAGTGGGCTCCGAGTGCTGCCCCAAGTGCAGTCCAGGTTATCGTGTGAAGGAGGCCTGCGGGGAGCTGACGGGCACAGTGTGTGAACCCTGCCCTCCAGGCACCTACATTGCCCACCTCAATGGCCTAAGCAAGTGTCTGCAGTGCCAAATGTGTGACCCAGCCATGGGCCTGCGCGCGAGCCGGAACTGCTCCAGGACAGAGAACGCCGTGTGTGGCTGCAGCCCAGGCCACTTCTGCATCGTCCAGGACGGGGACCACTGCGCCGCGTGCCGCGCTTACGCCACCTCCAGCCCGGGCCAGAGGGTGCAGAAGGGAGGCACCGAGAGTCAGGACACCCTGTGTCAGAACTGCCCCCCGGGGACCTTCTCTCCCAATGGGACCCTGGAGGAATGTCAGCACCAGACCAAGTGCAGCTGGCTGGTGACGAAGGCCGGAGCTGGGACCAGCAGCTCCCACTGGGTAATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 281) >Artificial Sequence; hHVEM-Fc-GPI, Amino AcidMEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKEDEYPVGSECCPKCSPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCDPAMGLRASRNCSRTENAVCGCSPGHFCIVQDGDHCAACRAYATSSPGQRVQKGGTESQDTLCQNCPPGTFSPNGTLEECQHQTKCSWLVTKAGAGTSSSHWVIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTL TGLLGTLVTMGLLT(SEQ ID NO: 282)hPDL1-GPI-P2A- >Artificial Sequence; hPDL1-GPI-P2A-hHVEM-GPI, DNAhHVEM-GPI ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGG CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTGGAAGCGGAGCTACTAACTTCAGCCTGCTGAAGCAGGCTGGCGACGTGGAGGAGAACCCTGGACCT ATGGAGCCTCCTGGAGACTGGGGGCCTCCTCCCTGGAGATCCACCCCCAAAACCGACGTCTTGAGGCTGGTGCTGTATCTCACCTTCCTGGGAGCCCCCTGCTACGCCCCAGCTCTGCCGTCCTGCAAGGAGGACGAGTACCCAGTGGGCTCCGAGTGCTGCCCCAAGTGCAGTCCAGGTTATCGTGTGAAGGAGGCCTGCGGGGAGCTGACGGGCACAGTGTGTGAACCCTGCCCTCCAGGCACCTACATTGCCCACCTCAATGGCCTAAGCAAGTGTCTGCAGTGCCAAATGTGTGACCCAGCCATGGGCCTGCGCGCGAGCCGGAACTGCTCCAGGACAGAGAACGCCGTGTGTGGCTGCAGCCCAGGCCACTTCTGCATCGTCCAGGACGGGGACCACTGCGCCGCGTGCCGCGCTTACGCCACCTCCAGCCCGGGCCAGAGGGTGCAGAAGGGAGGCACCGAGAGTCAGGACACCCTGTGTCAGAACTGCCCCCCGGGGACCTTCTCTCCCAATGGGACCCTGGAGGAATGTCAGCACCAGACCAAGTGCAGCTGGCTGGTGACGAAGGCCGGAGCTGGGACCAGCAGCTCCCACTGGGTA CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 283) >Artificial Sequence; hPDL1-GPI-P2A-hHVEM-GPI, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLTGSGATNFSLL KQAGDVEENPGPMEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKEDEYPVGSECCPKCSPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCDPAMGLRASRNCSRTENAVCGCSPGHFCIVQDGDHCAACRAYATSSPGQRVQKGGTESQDTLCQNCPPGTFSPNGTLEECQHQTKCSWINTKAGAGTSSSHWV PNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 284)mCTLA4-Fc-GPI >Artificial Sequence; mCTLA4-Fc-GPI, DNAATGGCTTGTCTTGGACTCCGGAGGTACAAAGCTCAACTGCAGCTGCCTTCTAGGACTTGGCCTTTTGTAGCCCTGCTCACTCTTCTTTTCATCCCAGTCTTCTCTGAAGCCATACAGGTGACCCAACCTTCAGTGGTGTTGGCTAGCAGCCATGGTGTCGCCAGCTTTCCATGTGAATATTCACCATCACACAACACTGATGAGGTCCGGGTGACTGTGCTGCGGCAGACAAATGACCAAATGACTGAGGTCTGTGCCACGACATTCACAGAGAAGAATACAGTGGGCTTCCTAGATTACCCCTTCTGCAGTGGTACCTTTAATGAAAGCAGAGTGAACCTCACCATCCAAGGACTGAGAGCTGTTGACACGGGACTGTACCTCTGCAAGGTGGAACTCATGTACCCACCGCCATACTTTGTGGGCATGGGCAACGGGACGCAGATTTATGTCATTGATCCAGAACCATGCCCGGATTCTGAATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 285) >Artificial Sequence; mCTLA4-Fc-GPI, Amino AcidMACLGLRRYKAQLQLPSRTWPFVALLTLLFIPVFSEAIQVTQPSVVLASSHGVASFPCEYSPSHNTDEVRVTVLRQTNDQMTEVCATTFTEKNTVGFLDYPFCSGTFNESRVNLTIQGLRAVDTGLYLCKVELMYPPPYFVGMGNGTQIYVIDPEPCPDSDIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 286)mPDL1-C1C2 >Artificial Sequence; mPDL1-C1C2, DNAATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTTACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATGGAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGGGAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCTCAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGAAATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGCATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCATACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTAATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCACCAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTCAATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACGTTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTGCCTGCAACACATCCTCCACAGAACAGGACTATCGATGTCGAGCCACTGGGCATGGAGAATGGGAACATTGCCAACTCACAGATCGCCGCCTCATCTGTGCGTGTGACCTTCTTGGGTTTGCAGCATTGGGTCCCGGAGCTGGCCCGCCTGAACCGCGCAGGCATGGTCAATGCCTGGACACCCAGCAGCAATGACGATAACCCCTGGATCCAGGTGAACCTGCTGCGGAGGATGTGGGTAACAGGTGTGGTGACGCAGGGTGCCAGCCGCTTGGCCAGTCATGAGTACCTGAAGGCCTTCAAGGTGGCCTACAGCCTTAATGGACACGAATTCGATTTCATCCATGATGTTAATAAAAAACACAAGGAGTTTGTGGGTAACTGGAACAAAAACGCGGTGCATGTCAACCTGTTTGAGACCCCTGTGGAGGCTCAGTACGTGAGATTGTACCCCACGAGCTGCCACACGGCCTGCACTCTGCGCTTTGAGCTACTGGGCTGTGAGCTGAACGGATGCGCCAATCCCCTGGGCCTGAAGAATAACAGCATCCCTGACAAGCAGATCACGGCCTCCAGCAGCTACAAGACCTGGGGCTTGCATCTCTTCAGCTGGAACCCCTCCTATGCACGGCTGGACAAGCAGGGCAACTTCAACGCCTGGGTTGCGGGGAGCTACGGTAACGATCAGTGGCTGCAGATCTTCCCTGGCAACTGGGACAACCACTCCCACAAGAAGAACTTGTTTGAGACGCCCATCCTGGCTCGCTATGTGCGCATCCTGCCTGTAGCCTGGCACAACCGCATCGCCCTGCGCCTGGAGCTGCTGGGCTGTTAG(SEQ ID NO: 287) >Artificial Sequence; mPDL1-C1C2, Amino AcidMRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYWEKEDEQVIQFVAGEEDLKPQHSNFSGRASLPKDQLLKGNAALQITDVKLQDAGVYCCIISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDHQPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPELPATHPPQNRTIDVEPLGMENGNIANSQIAASSVRVTFLGLQHWVPELARLNRAGMVNAWTPSSNDDNPWIQVNLLRRMWVTGVVTQGASRLASHEYLKAFKVAYSLNGHEFDFIHDVNKKHKEFVGNWNKNAVHVNLFETPVEAQYVRLYPTSCHTACTLRFELLGCELNGCANPLGLKNNSIPDKQITASSSYKTWGLHLFSWNPSYARLDKQGNFNAWVAGSYGNDQWLQIFPGNWDNHSHKKNLFETPILARYVRILPVAWHNRIALRLELLGC (SEQ ID NO: 288)mPDL1-Fc-GPI >Artificial Sequence; mPDL1-Fc-GPI, DNAATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTTACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATGGAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGGGAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCTCAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGAAATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGCATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCATACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTAATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCACCAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTCAATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACGTTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTGCCTGCAACACATCCTCCACAGAACAGGACTATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 289) >Artificial Sequence; mPDL1-Fc-GPI, Amino AcidMRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYWEKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCCIISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDHQPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVPYCTFWRSQPGQNHTAELIIPELPATHPPQNRTIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 290)mPDL1-GPI >Artificial Sequence; mPDL1-GPI, DNAATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTTACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATGGAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGGGAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCTCAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGAAATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGCATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCATACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTAATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCACCAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGAZAGAGGGGATGCTTCTCAATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACGTTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTGCCTGCAACACATCCTCCACAGAACAGGACT CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 291) >Artificial Sequence; mPDL1-GPI, Amino AcidMRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYWEKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCCIISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDHQPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 292)mPDL2-C1C2 >Artificial Sequence; mPDL2-C1C2, DNAATGCTGCTCCTGCTGCCGATACTGAACCTGAGCTTACAACTTCATCCTGTAGCAGCTTTATTCACCGTGACAGCCCCTAAAGAAGTGTACACCGTAGACGTCGGCAGCAGTGTGAGCCTGGAGTGCGATTTTGACCGCAGAGAATGCACTGAACTGGAAGGGATAAGAGCCAGTTTGCAGAAGGTAGAAAATGATACGTCTCTGCAAAGTGAAAGAGCCACCCTGCTGGAGGAGCAGCTGCCCCTGGGAAAGGCTTTGTTCCACATCCCTAGTGTCCAAGTGAGAGATTCCGGGCAGTACCGTTGCCTGGTCATCTGCGGGGCCGCCTGGGACTACAAGTACCTGACGGTGAAAGTCAAAGCTTCTTACATGAGGATAGACACTAGGATCCTGGAGGTTCCAGGTACAGGGGAGGTGCAGCTTACCTGCCAGGCTAGAGGTTATCCCCTAGCAGAAGTGTCCTGGCAAAATGTCAGTGTTCCTGCCAACACCAGCCACATCAGGACCCCCGAAGGCCTCTACCAGGTCACCAGTGTTCTGCGCCTCAAGCCTCAGCCTAGCAGAAACTTCAGCTGCATGTTCTGGAATGCTCACATGAAGGAGCTGACTTCAGCCATCATTGACCCTCTGAGTCGGATGGAACCCAAAGTCCCCAGAACGATCGATGTCGAGCCACTGGGCATGGAGAATGGGAACATTGCCAACTCACAGATCGCCGCCTCATCTGTGCGTGTGACCTTCTTGGGTTTGCAGCATTGGGTCCCGGAGCTGGCCCGCCTGAACCGCGCAGGCATGGTCAATGCCTGGACACCCAGCAGCAATGACGATAACCCCTGGATCCAGGTGAACCTGCTGCGGAGGATGTGGGTAACAGGTGTGGTGACGCAGGGTGCCAGCCGCTTGGCCAGTCATGAGTACCTGAAGGCCTTCAAGGTGGCCTACAGCCTTAATGGACACGAATTCGATTTCATCCATGATGTTAATAAAAAACACAAGGAGTTTGTGGGTAACTGGAACAAAAACGCGGTGCATGTCAACCTGTTTGAGACCCCTGTGGAGGCTCAGTACGTGAGATTGTACCCCACGAGCTGCCACACGGCCTGCACTCTGCGCTTTGAGCTACTGGGCTGTGAGCTGAACGGATGCGCCAATCCCCTGGGCCTGAAGAATAACAGCATCCCTGACAAGCAGATCACGGCCTCCAGCAGCTACAAGACCTGGGGCTTGCATCTCTTCAGCTGGAACCCCTCCTATGCACGGCTGGACAAGCAGGGCAACTTCAACGCCTGGGTTGCGGGGAGCTACGGTAACGATCAGTGGCTGCAGATCTTCCCTGGCAACTGGGACAACCACTCCCACAAGAAGAACTTGTTTGAGACGCCCATCCTGGCTCGCTATGTGCGCATCCTGCCTGTAGCCTGGCACAACCGCATCGCCCTGCGCCTGGAGCTGCTGGGCTGTTAG(SEQ ID NO: 293) >Artificial Sequence; mPDL2-C1C2, Amino AcidMLLLLPILNLSLQLHPVAALFTVTAPKEVYTVDVGSSVSLECDFDRRECTELEGIRASLQKVENDTSLQSERATLLEEQLPLGKALFHIPSVQVRDSGQYRCLVICGAAWDYKYLTVKVKASYMRIDTRILEVPGTGEVQLTCQARGYPLAEVSWQNVSVPANTSHIRTPEGLYQVTSVLRLKPQPSRNFSCMFWNAHMKELTSAIIDPLSRMEPKVPRTIDVEPLGMENGNIANSQIAASSVRVTFLGLQHWVPELARLNRAGMVNAWTPSSNDDNPWIQVNLLRRMWVTGVVTQGASRLASHEYLKAFKVAYSLNGHEFDFIHDVNKKHKEFVGNWNKNAVHVNLFETPVEAQYVRLYPTSCHTACTLRFELLGCELNGCANPLGLKNNSIPDKQITASSSYKTWGLHLFSWNPSYARLDKQGNFNAWVAGSYGNDQWLQIFPGNWDNHSHKKNLFETPILARYVRILPVAWHNRIALRLELLGC (SEQ ID NO: 294)mPDL2-Fc-GPI >Artificial Sequence; mPDL2-Fc-GPI, DNAATGCTGCTCCTGCTGCCGATACTGAACCTGAGCTTACAACTTCATCCTGTAGCAGCTTTATTCACCGTGACAGCCCCTAAAGAAGTGTACACCGTAGACGTCGGCAGCAGTGTGAGCCTGGAGTGCGATTTTGACCGCAGAGAATGCACTGAACTGGAAGGGATAAGAGCCAGTTTGCAGAAGGTAGAAAATGATACGTCTCTGCAAAGTGAAAGAGCCACCCTGCTGGAGGAGCAGCTGCCCCTGGGAAAGGCTTTGTTCCACATCCCTAGTGTCCAAGTGAGAGATTCCGGGCAGTACCGTTGCCTGGTCATCTGCGGGGCCGCCTGGGACTACAAGTACCTGACGGTGAAAGTCAAAGCTTCTTACATGAGGATAGACACTAGGATCCTGGAGGTTCCAGGTACAGGGGAGGTGCAGCTTACCTGCCAGGCTAGAGGTTATCCCCTAGCAGAAGTGTCCTGGCAAAATGTCAGTGTTCCTGCCAACACCAGCCACATCAGGACCCCCGAAGGCCTCTACCAGGTCACCAGTGTTCTGCGCCTCAAGCCTCAGCCTAGCAGAAACTTCAGCTGCATGTTCTGGAATGCTCACATGAAGGAGCTGACTTCAGCCATCATTGACCCTCTGAGTCGGATGGAACCCAAAGTCCCCAGAACGATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 295) >Artificial Sequence; mPDL2-Fc-GPI, Amino AcidMLLLLPILNLSLQLHPVAALFTVTAPKEVYTVDVGSSVSLECDFDRRECTELEGIRASLQKVENDTSLQSERATLLEEQLPLGKALFHIPSVQVRDSGQYRCLVICGAAWDYKYLTVKVKASYMRIDTRILEVPGTGEVQLTCQARGYPLAEVSWQNVSVPANTSHIRTPEGLYQVTSVLRLKPQPSRNFSCMFWNAHNKELTSAIIDPLSRMEPKVPRTIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 296)mPDL1-mFc-GPI >Artificial Sequence; mPDL1-mFc-GPI, DNAATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTTACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATGGAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGGGAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCTCAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGAAATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGCATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCATACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTAATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCACCAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTCAATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACGTTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTGCCTGCAACACATCCTCCACAGAACAGGACT GGTTGTAAGCCTTGCATATGTACAGTCCCAGAAGTATCATCTGTCTTCATCTTCCCCCCAAAGCCCAAGGATGTGCTCACCATTACTCTGACTCCTAAGGTCACGTGTGTTGTGGTAGACATCAGCAAGGATGATCCCGAGGTCCAGTTCAGCTGGTTTGTAGATGATGTGGAGGTGCACACAGCTCAGACGCAACCCCGGGAGGAGCAGTTCAACAGCACTTTCCGCTCAGTCAGTGAACTTCCCATCATGCACCAGGACTGGCTCAATGGCAAGGAGTTCAAATGCAGGGTCAACAGTGCAGCTTTCCCTGCCCCCATCGAGAAAACCATCTCCAAAACCAAAGGCAGACCGAAGGCTCCACAGGTGTACACCATTCCACCTCCCAAGGAGCAGATGGCCAAGGATAAAGTCAGTCTGACCTGCATGATAACAGACTTCTTCCCTGAAGACATTACTGTGGAGTGGCAGTGGAATGGGCAGCCAGCGGAGAACTACAAGAACACTCAGCCCATCATGGACACAGATGGCTCTTACTTCGTCTACAGCAAGCTCAATGTGCAGAAGAGCAACTGGGAGGCAGGAAATACTTTCACCTGCTCTGTGTTACATGAGGGCCTGCACAACCACCATACTGAGAAGAGCCTCTCCCAC TCTCCTGGTAAACCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGC TTGCTGACTTAG(SEQ ID NO: 297) >Artificial Sequence; mPDL1-mFc-GPI, Amino AcidMRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYWEKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCCIISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDHQPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSH SPGKPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 298)mPDL2-GPI >Artificial Sequence; mPDL2-GPI, DNAATGCTGCTCCTGCTGCCGATACTGAACCTGAGCTTACAACTTCATCCTGTAGCAGCTTTATTCACCGTGACAGCCCCTAAAGAAGTGTACACCGTAGACGTCGGCAGCAGTGTGAGCCTGGAGTGCGATTTTGACCGCAGAGAATGCACTGAACTGGAAGGGATAAGAGCCAGTTTGCAGAAGGTAGAAAATGATACGTCTCTGCAAAGTGAAAGAGCCACCCTGCTGGAGGAGCAGCTGCCCCTGGGAAAGGCTTTGTTCCACATCCCTAGTGTCCAAGTGAGAGATTCCGGGCAGTACCGTTGCCTGGTCATCTGCGGGGCCGCCTGGGACTACAAGTACCTGACGGTGAAAGTCAAAGCTTCTTACATGAGGATAGACACTAGGATCCTGGAGGTTCCAGGTACAGGGGAGGTGCAGCTTACCTGCCAGGCTAGAGGTTATCCCCTAGCAGAAGTGTCCTGGCAAAATGTCAGTGTTCCTGCCAACACCAGCCACATCAGGACCCCCGAAGGCCTCTACCAGGTCACCAGTGTTCTGCGCCTCAAGCCTCAGCCTAGCAGAAACTTCAGCTGCATGTTCTGGAATGCTCACATGAAGGAGCTGACTTCAGCCATCATTGACCCTCTGAGTCGGATGGAACCCAAAGTCCCCAGAACG CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 299) >Artificial Sequence; mPDL2-GPI, Amino AcidMLLLLPILNLSLQLHPVAALFTVTAPKEVYTVDVGSSVSLECDFDRRECTELEGIRASLQKVENDTSLQSERATLLEEQLPLGKALFHIPSVQVRDSGQYRCLVICGAAWDYKYLTVKVKASYMRIDTRILEVPGTGEVQLTCQARGYPLAEVSWQNVSVPANTSHIRTPEGLYQVTSVLRLKPQPSRNFSCMFWNAHMKELTSAIIDPLSRMEPKVPRT PNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 300)mPDL1-GPI-P2A- >Artificial Sequence; mPDL1-GPI-P2A-mHVEM-GPI, DNAmHVEM-GPI ATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTTACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATGGAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGGGAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCTCAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGAAATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGCATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCATACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTAATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCACCAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTCAATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACGTTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTGCCTGCAACACATCCTCCACAGAACAGGACT CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTGGAAGCGGAGCTACTAACTTCAGCCTGCTGAAGCAGGCTGGCGACGTGGAGGAGAACCCTGGACCTATGGAACCTCTCCCAGGATGGGGGTCGGCACCCTGGAGCCAGGCCCCTACAGACAACACCTTCAGGCTGGTGCCTTGTGTCTTCCTTTTGAACTTGCTGCAGCGCATCTCTGCCCAGCCCTCATGCAGACAGGAGGAGTTCCTTGTGGGAGACGAGTGCTGCCCCATGTGCAACCCAGGTTACCATGTGAAGCAGGTCTGCAGTGAGCATACAGGCACAGTGTGTGCCCCCTGTCCCCCACAGACATATACCGCCCATGCAAATGGCCTGAGCAAGTGTCTGCCCTGCGGAGTCTGTGATCCAGACATGGGCCTGCTGACCTGGCAGGAGTGCTCCAGCTGGAAGGACACTGTGTGCAGATGCATCCCAGGCTACTTCTGTGAGAACCAGGATGGGAGCCACTGTTCCACATGCTTGCAGCACACCACCTGCCCTCCAGGGCAGAGGGTAGAGAAGAGAGGGACTCACGACCAGGACACTGTATGTGCTGACTGCCTAACAGGGACCTTCTCACTTGGAGGGACTCAGGAGGAATGCCTGCCCTGGACCAACTGCAGTGCATTTCAACAGGAAGTAAGACGTGGGACCAACAGCACAGACACCACCTGCTCCTCCCAG CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG(SEQ ID NO: 301) >Artificial Sequence; mPDL1-GPI-P2A-mHVEM-GPI, Amino AcidMRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYWEKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCCIISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDHQPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLTGSGATNFSLL KQAGDVEENPGPMEPLPGWGSAPWSQAPTDNTFRLVPCVFLLNLLQRISAQPSCRQEEFLVGDECCPMCNPGYHVKQVCSEHTGTVCAPCPPQTYTAHANGLSKCLPCGVCDPDMGLLTWQECSSWKDTVCRCIPGYFCENQDGSHCSTCLQHTTCPPGQRVEKRGTHDQDTVCADCLTGTFSLGGTQEECLPWTNCSAFQQEVRRGTNSTDTTCSSQ PNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQ ID NO: 302)hPDL1-ADAM10 >Artificial Sequence; hPDL1-ADAM10, DNAATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGG TGTGGAAATGGAATGGTAGAACAAGGTGAAGAATGTGATTGTGGCTATAGTGACCAGTGTAAAGATGAATGCTGCTTCGATGCAAATCAACCAGAGGGAAGAAAATGCAAACTGAAACCTGGGAAACAGTGCAGTCCAAGTCAAGGTCCTTGTTGTACAGCACAGTGTGCATTCAAGTCAAAGTCTGAGAAGTGTCGGGATGATTCAGACTGTGCAAGGGAAGGAATATGTAATGGCTTCACAGCTCTCTGCCCAGCATCTGACCCTAAACCAAACTTCACAGACTGTAATAGGCATACACAAGTGTGCATTAATGGGCAATGTGCAGGTTCTATCTGTGAGAAATATGGCTTAGAGGAGTGTACGTGTGCCAGTTCTGATGGCAAAGATGATAAAGAATTATGCCATGTATGCTGTATGAAGAAAATGGACCCATCAACTTGTGCCAGTACAGGGTCTGTGCAGTGGAGTAGGCACTTCAGTGGTCGAACCATCACCCTGCAACCTGGATCCCCTTGCAACGATTTTAGAGGTTACTGTGATGTTTTCATGCGGTGCAGATTAGTAGATGCTGATGGTCCTCTAGCTAGGCTTAAAAAAGCAATTTTTAGTCCAGAGCTCTATGAAAACATTGCTGAATGGATTGTGGCTCATTGGTGGGCAGTATTACTTATGGGAATTGCTCTGATCATGCTAATGGCTGGATTTATTAAGATATGCAGTGTTaATACTCCAAGTAGTAATCCAAAGTTGCCTCCTCCTAAACCACTTCCAGGCACTTTAAAGAGGAGGAGACCTCCACAGCCCATTCAGCAACCCCAGCGTCAGCGGCCCCGAGAGAGTTATCAAATGGGACACATGAGACGCTAA(SEQ ID NO: 303) >Artificial Sequence; hPDL1-ADAM10, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKEPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERCGNGMVEQGEECDCGYSDQCKDECCFDANQPEGRKCKLKPGKQCSPSQGPCCTAQCAFKSKSEKCRDDSDCAREGICNGFTALCPASDPKPNFTDCNRHTQVCINGQCAGSICEKYGLEECTCASSDGKDDEELCHVCCMKKMDPSTCASTGSVQWSRHFSGRTITLQPGSPCNDFRGYCDVFMRCRLVDADGPLARLKKAIFSPELYENIAEWIVAHWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTLKRRRPPQPIQQPQR QRPRESYQMGHMRR(SEQ ID NO: 304) hPDL1-4Fc- >Artificial Sequence; hPDL1-4Fc-CD9tm2, DNACD9tm2 ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGG GAGTCCAAATATGGTCCCCCATGCCCATCATGCCCAGCACCTGAGTTCCTGGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGGGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGTAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGGACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCCGGGTAAA TTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGC(SEQ ID NO: 305) >Artificial Sequence; hPDL1-4Fc-CD9tm2, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVRVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEDNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHY TQKSLSLSPGKFYTGVYILIGAGALMMLVGFLGCCGAVQESQCVIM (SEQ ID NO: 306)hPDL1-4Fc- >Artificial Sequence; hPDL1-4Fc-CD9tm2-KRAS, DNA CD9tm2-ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT modified KRasACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGG GAGTCCAAATATGGTCCCCCATGCCCATCATGCCCAGCACCTGAGTTCCTGGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGGGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGTAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGGACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCCGGGTAAA TTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGC AAAAAGAAGAAAAAGAAGAAGAAGACAAAGTGTGTAATTATG TAA(SEQ ID NO: 307) >Artificial Sequence; hPDL1-4Fc-CD9tm2-KRAS, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVRVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEDNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHY TQKSLSLSPGKFYTGVYILIGAGALMMLVGFLGCCGAVQESQC KKKKKKKKTKCVIM (SEQ ID NO: 308)hPDL1-Fc- >Artificial Sequence; hPDL1-Fc-CD9tm2, DNA CD9tm2ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGGATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATTTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGCGTAATTATGTAA(SEQ ID NO: 309) >Artificial Sequence; hPDL1-Fc-CD9tm2, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPELPLAHPPNERIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDFYTGVYILIGAGALMMLVGFLGCCGAVQESQCVIM (SEQ ID NO: 310)hPDL1-Fc- >Artificial Sequence; hPDL1-Fc-CD9tm2-KRAS, DNA CD9tm2-ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT modified KRASACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTCTGGAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGGATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCQCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATTTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGC AAAAAGAAGAAAAAGAAGAAGAAGACAAAGTGTGTA ATTATGTAA  (SEQ ID NO: 311) >Artificial Sequence; hPDL1-Fc-CD9tm2-KRAS, Amino AcidMRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPELPLAHPPNERIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDFYTGVYILIGAGALMMLVGFLGCCGAVQESQC KKKKKKKKTKCV IM(SEQ ID NO: 312) mPDL1-mFc- >Artificial Sequence; mPDL1-mFc-CD9tm2, DNACD9tm2 ATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTTACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATGGAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGGGAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCTCAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGAAATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGCATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCATACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTAATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCACCAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTCAATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACGTTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTGCCTGCAACACATCCTCCACAGAACAGGACT GGTTGTAAGCCTTGCATATGTACAGTCCCAGAAGTATCATCTGTCTTCATCTTCCCCCCAAAGCCCAAGGATGTGCTCACCATTACTCTGACTCCTAAGGTCACGTGTGTTGTGGTAGACATCAGCAAGGATGATCCCGAGGTCCAGTTCAGCTGGTTTGTAGATGATGTGGAGGTGCACACAGCTCAGACGCAACCCCGGGAGGAGCAGTTCAACAGCACTTTCCGCTCAGTCAGTGAACTTCCCATCATGCACCAGGACTGGCTCAATGGCAAGGAGTTCAAATGCAGGGTCAACAGTGCAGCTTTCCCTGCCCCCATCGAGAAAACCATCTCCAAAACCAAAGGCAGACCGAAGGCTCCACAGGTGTACACCATTCCACCTCCCAAGGAGCAGATGGCCAAGGATAAAGTCAGTCTGACCTGCATGATAACAGACTTCTTCCCTGAAGACATTACTGTGGAGTGGCAGTGGAATGGGCAGCCAGCGGAGAACTACAAGAACACTCAGCCCATCATGGACACAGATGGCTCTTACTTCGTCTACAGCAAGCTCAATGTGCAGAAGAGCAACTGGGAGGCAGGAAATACTTTCACCTGCTCTGTGTTACATGAGGGCCTGCACAACCACCATACTGAGAAGAGCCTCTCCCAC TCTCCTGGTAAATTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGCGTAATT ATGTAA(SEQ ID NO: 313) >Artificial Sequence; mPDL1-mFc-CD9tm2, Amino AcidMRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYWEKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCCIISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDHQPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSH SPGKPFYTGVYILIGAGALMMLVGFLGCCGAVQESQCVIM (SEQ ID NO: 314)mPDL1-mFc- >Artificial Sequence; mPDL1-mFc-CD9tm2-KRAS, DNA CD9tm2-ATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTT modified KRASACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATGGAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGGGAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCTCAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGAAATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGCATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCATACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTAATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCACCAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTCAATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACGTTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTGCCTGCAACACATCCTCCACAGAACAGGACT GGTTGTAAGCCTTGCATATGTACAGTCCCAGAAGTATCATCTGTCTTCATCTTCCCCCCAAAGCCCAAGGATGTGCTCACCATTACTCTGACTCCTAAGGTCACGTGTGTTGTGGTAGACATCAGCAAGGATGATCCCGAGGTCCAGTTCAGCTGGTTTGTAGATGATGTGGAGGTGCACACAGCTCAGACGCAACCCCGGGAGGAGCAGTTCAACAGCACTTTCCGCTCAGTCAGTGAACTTCCCATCATGCACCAGGACTGGCTCAATGGCAAGGAGTTCAAATGCAGGGTCAACAGTGCAGCTTTCCCTGCCCCCATCGAGAAAACCATCTCCAAAACCAAAGGCAGACCGAAGGCTCCACAGGTGTACACCATTCCACCTCCCAAGGAGCAGATGGCCAAGGATAAAGTCAGTCTGACCTGCATGATAACAGACTTCTTCCCTGAAGACATTACTGTGGAGTGGCAGTGGAATGGGCAGCCAGCGGAGAACTACAAGAACACTCAGCCCATCATGGACACAGATGGCTCTTACTTCGTCTACAGCAAGCTCAATGTGCAGAAGAGCAACTGGGAGGCAGGAAATACTTTCACCTGCTCTGTGTTACATGAGGGCCTGCACAACCACCATACTGAGAAGAGCCTCTCCCAC TCTCCTGGTAAATTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGC AAAAAGAAGAAAAAGAAGAAGAAGACAAAGTGTGTAATTATGTAA(SEQ ID NO: 315) >Artificial Sequence; mPDL1-mFc-CD9tm2-KRAS, Amino AcidMRIFAGIIFTACCHLLRAFTITAPEDLYVVEYGSNVTMECRFPVERELDLLALVVYWEKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCCIISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDHQPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSH SPGKFYTGVYILIGAGALMMLVGFLGCCGAVQESQC KKKKKKKKTKCVIM (SEQ ID NO: 316)

In some embodiments of any of the aspects, the fusion polypeptidesprovided herein comprise two or more POI domains. The specificcombinations of POI domains can be used to regulate inflammatory immuneresponses. Non-limiting examples of additive and synergisticcombinations of POIs that can modulate inflammatory signaling pathwaysare provided in Table 5 (below).

TABLE 5 Exemplary POI combinations and combined targets for modulatinginflammation. COMBINED PUTATIVE ADDITIVE or POIs (LIGANDS) TARGETSSYNERGISTIC MOA PD-L1 or PD-L2 PD-1 Differential use of Shp HVEM BTLAphosphatases. BTLA inhibits both TCR and CD28 phosphorylation (via Shpl)while PD-1 inhibits CD28 phosphorylation (via Shp2). PD-L1 or PD-L2 PD-1LAG-3 exerts differential FGL1 LAG-3 inhibitory impacts on various typesof lymphocytes and shows synergy with PD-1 to inhibit immune responses.PD-L1 or PD-L2 PD-1 PD-1 and Tim-3 have non- CEACAM-1 or GAL9 TIM-3redundant downstream signaling mechanisms. PD-L1 or PD-L2 PD-1Differential use of Shp CD155 TIGIT phosphatases. Non-redundantlyregulate T cell responses. PD-L1 or PD-L2 PD-1 PD-1 and VISTA non- VSIG3VISTA redundantly regulate T cell responses. VISTA contains cytosolicSH3 binding domains for adapter proteins. CEACAM-1 or GAL9 TIM-3 TIGITand TIM-3 have non- CD155 TIGIT redundant downstream signalingmechanisms. PD-L1 or PD-L2 PD-1 PD-1, LAG-3 and TIM-3 have FGL1 LAG-3non-redundant downstream CEACAM-1 or GAL9 TIM-3 signaling mechanisms.

Methods of Preparing Extracellular Vesicle Compositions

In another aspect, provided herein is a method of preparing anengineered extracellular vesicle provided herein. Generally, the methodcomprises providing a population of cells expressing a vector constructencoding one or more sticky binder (vesicle targeting domain) and one ormore signaling domains (POI domain).

The EVs provided herein can be isolated and purified form any biologicalsource, e.g., cells. The cells that produce the engineered EVs providedherein can be from any viable non-human source or organism. Usually theorganism is an animal, vertebrate, or mammal. In some embodiments, thecell described herein is from a human. The cells described herein can befrom any tissue isolated from an organism by methods known in the art.The scientific literature provides guidance for one of ordinary skill inthe art to isolate, prepare, and culture cells as necessary for use inthe compositions and methods described herein. One of skill in the artcan appreciate that the cell source of the EVs may alter the cellularprotein expression and the native or endogenous cargo within the EV. Itis contemplated herein that this can be leveraged for therapeutic effectdepending on the disease or disorder being treated.

In some embodiments, the population of cells has been altered byexposure to environmental conditions (e.g., hypoxia), small moleculeaddition, presence/absence of exogenous factors (e.g., growth factors,cytokines) at the time, or substantially contemporaneous with, isolatingthe plurality of artificial synapses in a manner altering the regulatorystate of the cell. In various embodiments, the cells are HEK 293 cells,MSCs, PER.C, fibrosarcoma HT-1080 or HuH7 cell lines.

The method comprises providing a population of cells and culturing thecells in serum-free or un-concentrated conditioned medium. Thisincludes, for example, artificial synapses secreted into media asconditioned by a population of cells in culture, further including celllines capable of serial passaging. In certain embodiments, the cells inculture are grown to 10, 20, 30, 40, 50, 60, 70, 80, 90, or 90% or moreconfluency when artificial synapses (engineered EVs) are isolated.

The methods provided herein further comprise contacting the cellsprovided herein with a nucleic acid vector encoding the at least onefusion polypeptide provided herein. The vector can be added to the cellculture medium of the cells by methods known in the art and discussedfurther below.

A vector is a nucleic acid construct designed for delivery to a hostcell or for transfer of genetic material between different host cells.As used herein, a vector can be viral or non-viral. The term “vector”encompasses any genetic element that is capable of replication whenassociated with the proper control elements and that can transfergenetic material to cells. A vector can include, but is not limited to,a cloning vector, an expression vector, a plasmid, phage, transposon,cosmid, artificial chromosome, virus, virion, etc. In some embodimentsof any of the aspects, the vector is selected from the group consistingof: a plasmid, a cosmid and a viral vector.

“Expression” refers to the cellular processes involved in producing RNAand proteins and as appropriate, secreting proteins, including whereapplicable, but not limited to, for example, transcription, transcriptprocessing, translation and protein folding, modification andprocessing. “Expression products” include RNA transcribed from a gene,and polypeptides obtained by translation of mRNA transcribed from agene.

In some embodiments, a vector is capable of driving expression of one ormore sequences in a mammalian cell; i.e., the vector is a mammalianexpression vector. Examples of mammalian expression vectors includepCDM8 (Seed, 1987. Nature 329: 840) and pMT2PC (Kaufman, et al., 1987.EMBO J. 6: 187-195). When used in mammalian cells, the expressionvector's control functions are typically provided by one or moreregulatory elements. For example, commonly used promoters are derivedfrom polyoma, adenovirus 2, cytomegalovirus, simian virus 40, and othersdisclosed herein and known in the art. For other suitable expressionsystems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16and 17 of Sambrook, et al., MOLECULAR CLONING: A LABORATORY MANUAL. 2nded., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press,Cold Spring Harbor, N.Y., 1989.

In some embodiments, the recombinant expression vector is capable ofdirecting expression of the exogenous fusion polypeptide nucleic acidsequence preferentially in a particular cell type (e.g., viatissue-specific regulatory elements).

Tissue-specific and inducible regulatory elements are known in the art.Non-limiting examples of suitable tissue-specific promoters include thealbumin promoter (liver-specific; Pinkert, et al., 1987. Genes Dev. 1:268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv.hnmunol. 43: 235-275), in particular promoters of T cell receptors(Winoto and Baltimore, 1989. EMBO J. 8: 729-733) and immunoglobulins(Baneiji, et al., 1983. Cell 33: 729-740; Queen and Baltimore, 1983.Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilamentpromoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86:5473-5477), pancreas-specific promoters (Edlund, et al., 1985. Science230: 912-916), and mammary gland-specific promoters (e.g., milk wheypromoter; U.S. Pat. No. 4,873,316 and European Application PublicationNo. 264,166). Developmentally-regulated promoters are also encompassed,e.g., the murine hox promoters (Kessel and Gruss, 1990. Science 249:374-379) and the α-fetoprotein promoter (Campes and Tilghman, 1989.Genes Dev. 3: 537-546).

In some embodiments, the at least one nucleic acid sequence describedherein is delivered to the cell described herein via an integratingvector. Integrating vectors have their delivered genetic material (or acopy of it) permanently incorporated into a host cell chromosome.Non-integrating vectors remain episomal which means the nucleic acidcontained therein is never integrated into a host cell chromosome.Examples of integrating vectors include retroviral vectors, lentiviralvectors, hybrid adenoviral vectors, and herpes simplex viral vectors.

In some embodiments, the at least one nucleic acid sequence describedherein is delivered to the cell described herein via a non-integrativevector. Non-integrative vectors include non-integrative viral vectors.Non-integrative viral vectors eliminate one of the primary risks posedby integrative retroviruses, as they do not incorporate their genomeinto the host DNA. One example is the Epstein Barr oriP/NuclearAntigen-1 (“EBNA1”) vector, which is capable of limited self-replicationand known to function in mammalian cells. Containing two elements fromEpstein-Barr virus, oriP and EBNA1, binding of the EBNA1 protein to thevirus replicon region oriP maintains a relatively long-term episomalpresence of plasmids in mammalian cells. This particular feature of theoriP/EBNA1 vector makes it ideal for generation of integration-free hostcells. Other non-integrative viral vectors include adenoviral vectorsand the adeno-associated viral (AAV) vectors.

Another non-integrative viral vector is RNA Sendai viral vector, whichcan produce protein without entering the nucleus of an infected cell.The F-deficient Sendai virus vector remains in the cytoplasm of infectedcells for a few passages, but is diluted out quickly and completely lostafter several passages (e.g., 10 passages). This permits a self-limitingtransient expression of a chosen heterologous gene or genes in a targetcell. This aspect can be helpful, e.g., for the transient introductionof reprogramming factors, among other uses. As noted above, in someembodiments, the nucleic acid sequence described herein is expressed inthe cells from a viral vector.

A “viral vector” includes a nucleic acid vector construct that includesat least one element of viral origin and has the capacity to be packagedinto a viral vector particle. The viral vector can contain a nucleicacid encoding a polypeptide described herein in place of non-essentialviral genes. The vector and/or particle can be utilized for the purposeof transferring nucleic acids into cells either in vitro or in vivo.

The nucleic acids described herein can be delivered using anytransfection reagent or other physical means that facilitates entry ofnucleic acids into a cell. Methods of non-viral delivery of nucleicacids include lipofection, nucleofection, microinjection,electroporation, biolistics, virosomes, liposomes, immunoliposomes,polycation or lipid:nucleic acid conjugates, naked DNA, artificialvirions, and agent-enhanced uptake of DNA. Lipofection is described ine.g., U.S. Pat. Nos. 5,049,386, 4,946,787; and 4,897,355) andlipofection reagents are sold commercially (e.g., Transfectam™ andLipofectin™). Cationic and neutral lipids that are suitable forefficient receptor-recognition lipofection of polynucleotides includethose of Feigner, WO 91/17424; WO 91/16024. Delivery can be to cells(e.g. in vitro or ex vivo administration) or target tissues (e.g. invivo administration).

The preparation of lipid:nucleic acid complexes, including targetedliposomes such as immunolipid complexes, is well known to one of skillin the art (see, e.g., Crystal, Science 270:404-410 (1995); Blaese etal., Cancer Gene Ther. 2:291-297 (1995); Behr et al., Bioconjugate Chem.5:382-389 (1994); Remy et al., Bioconjugate Chem. 5:647-654 (1994); Gaoet al., Gene Therapy 2:710-722 (1995); Ahmad et al., Cancer Res.52:4817-4820 (1992); U.S. Pat. Nos. 4,186,183, 4,217,344, 4,235,871,4,261,975, 4,485,054, 4,501,728, 4,774,085, 4,837,028, and 4,946,787).

An “agent that increases cellular uptake” is a molecule that facilitatestransport of a molecule, e.g., nucleic acid, or peptide or polypeptide,or other molecule that does not otherwise efficiently transit the cellmembrane across a lipid membrane. For example, a nucleic acid can beconjugated to a lipophilic compound (e.g., cholesterol, tocopherol,etc.), a cell penetrating peptide (CPP) (e.g., penetratin, TAT, Syn1B,etc.), or a polyamine (e.g., spermine). Further examples of agents thatincrease cellular uptake are disclosed, for example, in Winkler (2013).Oligonucleotide conjugates for therapeutic applications. Ther. Deliv.4(7); 791-809. The one or more nucleic acid sequences encoding thefusion polypeptides provided herein can be delivered to the cell by anymethod discussed above or known in the art.

In some embodiments of any of the aspects, the vectors provided hereincomprise a nucleic acid modification by methods known in the art. Insome embodiments, the cell can be genetically manipulated to express oneor more vectors, each encoding one or more vesicle targeting domainsand/or one or more signaling domains. In certain embodiments, thepopulation of cells has been genetically manipulated. This includes, forexample, knockout (KO) or transgenic (TG) cell lines, wherein anendogenous gene has been removed and/or an exogenous introduced in astable, persistent manner. In certain embodiments, this further includestransient knockdown of one or more genes and associated coding andnon-coding transcripts within the population of cells, via any number ofmethods known in the art, such as introduction of dsRNA, siRNA,microRNA, etc. This further includes transient expression of one or moregenes and associated coding and non-coding transcripts within thepopulation of cells, via any number of methods known in the art, such asintroduction of a vector, plasmid, artificial plasmid, replicativeand/or non-replicative virus, etc.

In certain embodiments the cell population has been manipulated toknockout the expression of one or more endogenous gene sequences thatencode for metalloendopeptidases. In certain embodiments the cellpopulation has been manipulated to knockout the expression of one ormore endogenous gene sequences that code for metalloproteinases. Incertain embodiments the cell population has been manipulated to knockoutthe expression of one or more endogenous gene sequences that encode fora disintegrin and metalloproteinase (ADAM). For example, the cellpopulation can be manipulated to knock of the expression of one or moregene sequences that encode for ADAM1, ADAM2, ADAM7, ADAMS, ADAM9,ADAM10, ADAM11, ADAM12, ADAM15, ADAM17, ADAM18, ADAM19, ADAM20, ADAM21,ADAM22, ADAM23, ADAM28, ADAM29, ADAM30, ADAM33, etc.

In certain embodiments the cell population has been manipulated toknockout the expression of one or more endogenous genes that encode forenzymes that hydrolyze the inositol phosphate linkage in proteinsanchored by phosphatidylinositol glycans, thereby preventing the releaseof proteins attached to the plasma membrane via GPI anchors. Forexample, the cell population can be manipulated to knock of theexpression of phosphatidylinositol-glycan-specific phospholipase D(GPLD1).

In certain embodiments, the population of cells has been geneticallymanipulated. This includes, for example, knock-in of an exogenousgenetic sequence, wherein the exogenous genetic sequence is expressed ina stable, persistent manner. In certain embodiments, the cell populationhas been manipulated to knock-in recombinase recognition sequences(e.g., FRT), transgenic reporters such as antibiotic resistance genes,fluorescent or enzymatic reporter genes, etc. or the like.

In some embodiments, the method comprises a step of isolating theengineered extracellular vesicles provided herein. Particulates withinthe medium are removed by a series of specific centrifugation steps andthe media is filtered. The general method of isolating extracellularvesicles as provided herein is depicted in FIG. 21 of the workingexamples. Methods of isolating and purifying the extracellular vesiclesand exosomes are known in the art and further described, e.g., inWhitford W, Guterstam P. Exosome manufacturing status. Future Med Chem.2019 May; 11(10):1225-1236. doi: 10.4155/fmc-2018-0417. PMID: 31280675,Patel D B, Santoro M, Born U, Fisher J P, Jay S M. Towards rationallydesigned biomanufacturing of therapeutic extracellular vesicles: impactof the bioproduction microenvironment. Biotechnol Adv. 2018 December;36(8):2051-2059. doi: 10.1016/j.biotechadv.2018.09.001. Epub 2018 Sep.12. PMID: 30218694; PMCID: PMC6250573, Ng K S, Smith J A, McAteer M P,Mead B E, Ware J, Jackson F O, Carter A, Ferreira L, Bure K, Rowley J A,Reeve B, Brindley D A, Karp J M. Bioprocess decision support tool forscalable manufacture of extracellular vesicles. Biotechnol Bioeng. 2019February; 116(2):307-319. doi: 10.1002/bit.26809. Epub 2018 Nov. 8.PMID: 30063243; PMCID: PMC6322973, Paganini C, Capasso Palmiero U,Pocsfalvi G, Touzet N, Bongiovanni A, Arosio P. Scalable Production andIsolation of Extracellular Vesicles: Available Sources and Lessons fromCurrent Industrial Bioprocesses. Biotechnol J. 2019 October;14(10):e1800528. doi: 10.1002/biot.201800528. Epub 2019 Jul. 8. PMID:31140717, which are incorporated herein by reference in theirentireties.

In some embodiments, isolating the plurality of engineered EVs(artificial synapses) includes precipitation, centrifugation,filtration, immuno-separation, tangential flow, liquid chromatography,and/or flow fractionation. For example, differential ultracentrifugationhas become a technique wherein secreted exosomes are isolated from thesupernatants of cultured cells. This approach allows for separation ofexosomes from non-membranous particles, by exploiting their relativelylow buoyant density. Size exclusion allows for their separation frombiochemically similar, but biophysically different microvesicles, whichpossess larger diameters of up to 1,000 nm. Differences in floatationvelocity further allows for separation of differentially sized exosomes.In general, exosome sizes will possess a diameter ranging from 30-300nm, including sizes of 30-150 nm. Further purification may rely onspecific properties of the particular exosomes of interest. Thisincludes, for example, use of immunoadsorption with a protein ofinterest to select specific vesicles with exoplasmic or outwardorientations.

Among current methods (differential centrifugation, discontinuousdensity gradients, immunoaffinity, ultrafiltration and liquidchromatography (e.g., fast protein liquid chromatography (FPLC)),differential ultracentrifugation is the most commonly used for exosomeisolation. This technique utilizes increasing centrifugal force from2000×g to 10,000×g to separate the medium- and larger-sized particlesand cell debris from the exosome pellet at 100,000×g. Centrifugationalone allows for significant separation/collection of exosomes from aconditioned medium, although it is insufficient to remove variousprotein aggregates, genetic materials, particulates from media and celldebris that are common contaminants. Enhanced specificity of exosomepurification may deploy sequential centrifugation in combination withultrafiltration, or equilibrium density gradient centrifugation in asucrose density gradient, to provide for the greater purity of theexosome preparation (flotation density 1.1-1.2 g/ml) or application of adiscrete sugar cushion in preparation.

Ultrafiltration can be used to purify exosomes without compromisingtheir biological activity. Membranes with different pore sizes—such as100 kDa molecular weight cut-off (MWCO) or 300 kDa MWCO and gelfiltration to eliminate smaller particles—have been used to avoid theuse of a nonneutral pH or non-physiological salt concentration.Currently available tangential flow filtration (TFF) systems arescalable (to >10,000 L), allowing one to not only purify, butconcentrate the exosome fractions, and such approaches are less timeconsuming than differential centrifugation. Liquid Chromatography canalso be used to purify exosomes to homogeneously sized particles andpreserve their biological activity as the preparation is maintained at aphysiological pH and salt concentration.

Other chemical methods have exploit differential solubility of exosomesfor precipitation techniques, addition to volume-excluding polymers(e.g., polyethylene glycols (PEGs)), possibly combined additional roundsof centrifugation or filtration. For example, a precipitation reagent,ExoQuick®, can be added to conditioned cell media to quickly and rapidlyprecipitate a population of exosomes, although re-suspension of pelletsprepared via this technique may be difficult. Flow field-flowfractionation (FlFFF) is an elution-based technique that is used toseparate and characterize macromolecules (e.g., proteins) and nano- tomicro-sized particles (e.g., organelles and cells) and which has beensuccessfully applied to fractionate exosomes from culture media.

Beyond these techniques relying on general biochemical and biophysicalfeatures, focused techniques may be applied to isolated specificexosomes of interest. This includes relying on antibody immunoaffinityto recognizing certain exosome-associated antigens. Conjugation tomagnetic beads, chromatography matrices, plates or microfluidic devicesallows isolating of specific exosome populations of interest as may berelated to their production from a parent cell of interest or associatedcellular regulatory state. Other affinity-capture methods use lectinswhich bind to specific saccharide residues on the exosome surface.

In several embodiments, isolating a plurality of artificial synapsesfrom the population of cells includes centrifugation of the cells and/ormedia conditioned by the cells. In several embodiments,ultracentrifugation is used. In several embodiments, isolating aplurality of artificial synapses from the population of cells is viasize-exclusion filtration. In other embodiments, isolating a pluralityof artificial synapses from the population of cells includes use ofdiscontinuous density gradients, immunoaffinity, ultrafiltration,tangential flow and/or liquid chromatography.

In certain embodiments, differential ultracentrifugation includes usingcentrifugal force from 1000-2000×g, 2000-3000×g, 3000-4000×g,4000-5000×g, 5000×g-6000×g, 6000-7000×g, 7000-8000×g, 8000-9000×g,9000-10,000×g, to 10,000×g or more to separate larger-sized particlesfrom a plurality of artificial synapses derived from the cells.

In other embodiments, isolating a plurality of artificial synapses fromthe population of cells includes use of filtration or ultrafiltration.In certain embodiments, a size exclusion membrane with different poresizes is used. For example, a size exclusion membrane can include use ofa filter with a pore size of 0.1-0.5 micron (μm), 0.5-1.0 μm, 1-2.5 μm,2.5-5 μm, 5 or more μm. In certain embodiments, the pore size is about0.2 In certain embodiments, filtration or ultrafiltration includes sizeexclusion ranging from 100-500 daltons (Da), 500-1 kDa, 1-2 kDa, 2-5kDa, 5-10 kDa, 10-25 kDa, 25-50 kDa, 50-100 kDa, 100-250 kDa, 250-500kDa, 500 or more kDa. In certain embodiments, the size exclusion is forabout 2-5 kDa. In certain embodiments, the size exclusion is for about 3kDa. In other embodiments, filtration or ultrafiltration includes sizeexclusion includes use of hollow fiber membranes capable of isolatingparticles ranging from 100-500 daltons (Da), 500-1 kDa, 1-2 kDa, 2-5kDa, 5-10 kDa, 10-25 kDa, 25-50 kDa, 50-100 kDa, 100-250 kDa, 250-500kDa, 500 or more kDa. In certain embodiments, the size exclusion is forabout 2-5 kDa. In certain embodiments, the size exclusion is for about 3kDa. In other embodiments, a molecular weight cut-off (MWCO) gelfiltration capable of isolating particles ranging from 100-500 daltons(Da), 500-1 kDa, 1-2 kDa, 2-5 kDa, 5-10 kDa, 10-25 kDa, 25-50 kDa,50-100 kDa, 100-250 kDa, 250-500 kDa, 500 or more kDa. In certainembodiments, the size exclusion is for about 2-5 kDa. In certainembodiments, the size exclusion is for about 3 kDa. In variousembodiments, such systems are used in combination with variable fluidflow systems. In certain embodiments, a size exclusion membrane withdifferent pore sizes is used to purify extracellular vesicles from asolution comprising undesirable proteins or nucleic acids.

In other embodiments, isolating a plurality of artificial synapses fromthe population of cells includes use of tangential flow filtration (TFF)systems are used purify and/or concentrate the exosome fractions. Inother embodiments, isolating a plurality of artificial synapses from thepopulation of cells includes use of liquid chromatography can also beused to purify artificial synapses to homogeneously sized particles. Invarious embodiments, density gradients as used, such as centrifugationin a sucrose density gradient or application of a discrete sugar cushionin preparation.

In other embodiments, isolating a plurality of artificial synapses fromthe population of cells includes use of a precipitation reagent. Forexample, a precipitation reagent, ExoQuick®, can be added to conditionedcell media to quickly and rapidly precipitate a population of artificialsynapses. In other embodiments, isolating a plurality of artificialsynapses from the population of cells includes use of volume-excludingpolymers (e.g., polyethylene glycols (PEGS)) are used. In anotherembodiment, isolating a plurality of artificial synapses from thepopulation of cells includes use of flow field-flow fractionation(FlFFF), an elution-based technique.

In certain embodiments, isolating a plurality of artificial synapsesfrom the population of cells includes use of one or more capture agentsto isolate one or more artificial synapses possessing specificbiomarkers or containing particular biological molecules. In oneembodiment, one or more capture agents include at least one antibody.For example, antibody immunoaffinity recognizing exosome-associatedantigens is used to capture specific artificial synapses. In otherembodiments, the at least one antibody are conjugated to a fixedsurface, such as magnetic beads, chromatography matrices, plates ormicrofluidic devices, thereby allowing isolation of the specific exosomepopulations of interest. In other embodiments, isolating a plurality ofartificial synapses from the population of cells includes use of one ormore capture agents that is not an antibody. This includes, for example,use of a “bait” molecule presenting an antigenic feature complementaryto a corresponding molecule of interest on the exosome surface, such asa receptor or other coupling molecule. In one embodiment, thenon-antibody capture agent is a lectin capable of binding topolysaccharide residues on the exosome surface.

In other embodiments, isolating a plurality of artificial synapses fromthe population of cells includes use of ion exchange chromatography. Inother embodiments, isolating a plurality of artificial synapses from thepopulation of cells includes use of anion exchange chromatography. Inother embodiments, isolating a plurality of artificial synapses from thepopulation of cells includes use of caion exchange chromatography. Incertain embodiments, ion exchange chromatography comprises achromatography resin with a functional group selected from the groupconsisting of diethylaminoethyl (DEAE), quaternary aminoethyl (QAE),quaternary ammonium (Q), carboxymethyl (CM), sulfopropyl (SP), or methylsulfate (S). In certain embodiments, ion exchange chromatographycomprises a chromatography resin which may have properties of a weakacid, strong acid, weak base, or strong basic. In certain embodiments,ion exchange chromatography comprises a chromatography selected from thegroup consisting of DEAE cellulose, DEAE Sephadex, Mono Q, Mini Q,HiTrap Capto, Capto Core 700, HiPrep Q, QAE Sephadex, Q Sepharose, CMCellulose, SP Sepharose, SOURCE S, EAH-Sepharose, sulfoxyethylcellulose, CM Sephadex, or CM Sepharose. Isolating a plurality ofartificial synapses can be prepared by any of a variety of ion exchangechromatography techniques that are known in the art.

In other embodiments, isolating a plurality of artificial synapses fromthe population of cells includes use of a nuclease enzyme (e.g., a DNaseor RNase). For example, a working concentration of Benzonase® nucleasemay be added to an extracellular vesicle sample preparation in thepresence of a divalent cation, for example 1-2 mM Mg2⁺, 2-5 mM Mg2⁺,10-20 mM Mg2⁺, 20-50 mM Mg2⁺, 50-100 mM Mg2⁺, or more than 100 mM Mg2⁺.

Following isolation and purification of the engineered EVs providedherein, EVs can be further evaluated for the desired structural andfunctional properties by methods known in the art. For example, theengineered exosomes provided herein can be assayed for functionalactivity on a target cell using a cell-based bioassays (e.g., thosecommercially available, Promega DiscoverX®), ligand-receptor bindingassays, vesicle flow cytometric assays, enzyme-linked immunosorbentassays, tunable resistive pulse sensing (TRPS), nanoparticle trackinganalysis (NTA), surface plasmon resonance (SSPR), nucleotide sequencing,lipidomics, proteomics, colorimetric assays, fluorescence assays,luminescence assays, immunoblotting, radioimmunoassays, electronmicroscopy, or EV automated analysis (e.g., Exoview®). Additionalmethods of characterizing EVs are found, e.g., in Zhang Y, Bi J, HuangJ, Tang Y, Du S, Li P. Exosome: A Review of Its Classification,Isolation Techniques, Storage, Diagnostic and Targeted TherapyApplications. Int J Nanomedicine. 2020 Sep. 22; 15:6917-6934. doi:10.2147/UN.S264498. PMID: 33061359; PMCID: PMC7519827, Kluszczyńska K,Czernek L, Cypryk W, Pęczek L, Düchler M. Methods for the Determinationof the Purity of Exosomes. Curr Pharm Des. 2019; 25(42):4464-4485. doi:10.2174/1381612825666191206162712. PMID: 31808383, Nolan J P, Duggan E.Analysis of Individual Extracellular Vesicles by Flow Cytometry. MethodsMol Biol. 2018; 1678:79-92. doi: 10.1007/978-1-4939-7346-0_5. PMID:29071676.; Doyle L M, Wang M Z. Overview of Extracellular Vesicles,Their Origin, Composition, Purpose, and Methods for Exosome Isolationand Analysis. Cells. 2019 Jul. 15; 8(7):727. doi: 10.3390/cells8070727.PMID: 31311206; PMCID: PMC6678302, Pugholm L H, Revenfeld A L,Sondergaard E K, Jorgensen M M. Antibody-Based Assays for Phenotyping ofExtracellular Vesicles. Biomed Res Int. 2015; 2015:524817. doi:10.1155/2015/524817. Epub 2015 Dec. 3. PMID: 26770974; PMCID:PMC4681819, Shao H, Im H, Castro C M, Breakefield X, Weissleder R, LeeH. New Technologies for Analysis of Extracellular Vesicles. Chem Rev.2018 Feb. 28; 118(4):1917-1950. doi: 10.1021/acs.chemrev.7b00534. Epub2018 Jan. 31. PMID: 29384376; PMCID: PMC6029891, which are incorporatedherein by reference in their entireties.

Pharmaceutical Compositions

Provided herein are compositions comprising the engineered extracellularvesicles (artificial synapses) provided herein.

In one aspect, provided herein is a composition comprising: a pluralityof the engineered extracellular vesicles provided herein. In someembodiments of any of the aspects, the compositions and engineered EVsprovided herein further comprise a pharmaceutically acceptable carrier.

For clinical use of the methods and compositions described herein,administration of the engineered EVs/artificial synapses provided hereincan include formulation into pharmaceutical compositions orpharmaceutical formulations for parenteral administration, e.g.,intravenous; mucosal, e.g., intranasal; ocular, or other mode ofadministration. In some embodiments, the engineered EVs described hereincan be administered along with any pharmaceutically acceptable carriercompound, material, or composition which results in an effectivetreatment in the subject. Thus, a pharmaceutical formulation for use inthe methods described herein can contain the engineered EVs describedherein in combination with one or more pharmaceutically acceptableingredients. The phrase “pharmaceutically acceptable” refers to thosecompounds, materials, compositions, and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of human beings and animals without excessive toxicity,irritation, allergic response, or other problem or complication,commensurate with a reasonable benefit/risk ratio. The phrase“pharmaceutically acceptable carrier” as used herein means apharmaceutically acceptable material, composition or vehicle, such as aliquid or solid filler, diluent, excipient, solvent, media,encapsulating material, manufacturing aid (e.g., lubricant, talcmagnesium, calcium or zinc stearate, or steric acid), or solventencapsulating material, involved in maintaining the stability,solubility, or activity of, an engineered EV as described herein. Eachcarrier must be “acceptable” in the sense of being compatible with theother ingredients of the formulation and not injurious to the patient.The terms “excipient,” “carrier,” “pharmaceutically acceptable carrier”or the like are used interchangeably herein.

The engineered EVs provided herein can be formulated for administrationof the compound to a subject in solid, liquid, or gel form, includingthose adapted for the following: (1) parenteral administration, forexample, by subcutaneous, intramuscular, intravenous or epiduralinjection as, for example, a sterile solution or suspension, orsustained-release formulation; (2) transdermally; (3) transmucosally;(4) via bronchoalveolar lavage.

In some embodiments, the compositions described herein comprise aparticle or polymer-based vehicle. Exemplary particle or polymer-basedvehicles include, but are not limited to, nanoparticles, microparticles,polymer microspheres, or polymer-drug conjugates.

In one embodiment of any of the aspects, the compositions describedherein further comprise a lipid vehicle. Exemplary lipid vehiclesinclude, but are not limited to, liposomes, phospholipids, micelles,lipid emulsions, and lipid-drug complexes.

Formulations can be adapted for delivery to the airway, e.g., to addressrespiratory inflammation. Such formulations can be adapted for deliveryas an aerosol, e.g., for inhalation. In some embodiments, thecompositions described herein are formulated for aerosol administration,nebulizer administration, tracheal lavage administration, or for apulmonary delivery device.

As used herein, the term “pulmonary delivery device” refers to a deviceused to deliver a therapeutic dose of a composition of the presentinvention to the respiratory system including, but not limited to, anebulizer, metered-dose inhaler, or dry powder inhaler.

Examples of nebulizers include, but are not limited to, soft mistinhalers (for example Respimat® Boehringer Ingelheim) jet nebulizers(use compressed gas or air), ultrasonic nebulizers (produce aerosolsusing a piezoelectric crystal vibrating at high frequencies), andvibrating mesh nebulizers.

As used herein, the term “jet nebulizer” refers to a device that flowscompressed air or gas through a composition of the present invention foraerosolization. The aerosolized composition of the present invention maybe inhaled by a patient. Jet nebulizer may include, but is not limitedto, jet nebulizers with a corrugated tube, jet nebulizers with acollection bag, breath enhanced jet nebulizers, breath actuated jetnebulizers, and metered-dose inhalers. Examples of jet nebulizersinclude, but are not limited to, Circulaire (Westmed INC, Tucson,Ariz.), Pari Inhalierboy (PARI, Midlothian, Va.), Pari LC Plus (PARI,Midlothian, Va.), NebuTech (Salter Labs, Arvin, Calif.), AeroEclipse(Monoghan/Trudell Medical International, London, Ontario, Canada), andMaxin MA-2 (MA-2; Clinova Medical AB, Malmo, Sweden). Examples ofultrasonic nebulizers include, but are not limited to,DeVilbiss-Pulmosonic (Somerset, Pa.), Omron-Microair (Omron, Kyoto,Japan), Omron NE-U17 (Omron, Kyoto, Japan), Rhone Poulenc-Rorer-Fisoneb(Sanofi, Paris, France), and Beurer Nebulizer IH30 (Beurer GmbH,Neu-Ulm, Germany).

As used herein, the term “mesh nebulizer” refers to forcing a liquid,gel, fluid, solution, tincture, or the like through apertures in a meshor aperture plate to generate aerosol. Mesh nebulizer may include, butis not limited to, active mesh nebulizers and passive mesh nebulizers.Examples of active mesh nebulizers include, but is not limited to,Aeroneb® (Aerogen, Galway, Ireland) and eFlow® (PARI, Midlothian, Va.).Examples of passive mesh nebulizers are, but not limited to, I-neb(Philips Respironics, Newark, USA), AKITA (Activaero, Gemunden/Wohra,Germany), and Microair NE-U22® (Omron, Kyoto, Japan).

For use as aerosols, the compositions described herein can be preparedin a solution or suspension and may be packaged in a pressurized aerosolcontainer together with suitable propellants, for example, hydrocarbonpropellants like propane, butane, or isobutane with conventionalexcipients.

The engineered EVs provided herein can also be administered in anon-pressurized form such as in a nebulizer or atomizer that reduces aliquid to a fine spray. Preferably, by such nebulization small liquiddroplets of uniform size are produced from a larger body of liquid in acontrolled manner. Nebulization can be achieved by any suitable meanstherefor, including by using many nebulizers known and marketed today.For example, an AEROMIST™ pneumatic nebulizer available from InhalationPlastic, Inc. of Niles, Ill.

When the active ingredients are adapted to be administered, eithertogether or individually, via nebulizer(s) they can be in the form of anebulized aqueous suspension or solution, with or without a suitable pHor tonicity adjustment, either as a unit dose or multi-dose device.

Furthermore, any suitable gas can be used to apply pressure during thenebulization, with preferred gases to date being those which arechemically inert. Exemplary gases including, but are not limited to,nitrogen, argon, or helium can be used to advantage.

In some embodiments, the compositions described herein can also beadministered directly to the airways in the form of a dry powder. Thus,the engineered EVs can be administered via an inhaler. Exemplaryinhalers include metered dose inhalers and dry powdered inhalers.

A metered dose inhaler or “MDI” is a pressure resistant canister orcontainer filled with a product such as a pharmaceutical compositiondissolved in a liquefied propellant or micronized particles suspended ina liquefied propellant. The propellants which can be used includechlorofluorocarbons, hydrocarbons or hydrofluoroalkanes. Commonly usedpropellants are P134a (tetrafluoroethane) and P227 (heptafluoropropane)each of which may be used alone or in combination. They are optionallyused in combination with one or more other propellants and/or one ormore surfactants and/or one or more other excipients, for exampleethanol, a lubricant, an anti-oxidant and/or a stabilizing agent.

As used herein, the term “dry powder inhaler” refers to a device thatdelivers a therapeutic dose of a composition of the present invention ina powdered form without propellants to the respiratory system. A drypowder inhaler (i.e., Turbuhaler™ (Astra AB)) is a system operable witha source of pressurized air to produce dry powder particles of apharmaceutical composition that is compacted into a very small volume.Examples of dry powder inhalers include, but are not limited to,Spinhaler® (Fisons Pharmaceuticals, Rochester, N.Y.), Rotahaler®(GlaxoSmithKline, NC), Turbuhaler® (AstraZeneca, UK), and Diskhaler®(GlaxoSmithKline, NC).

Dry powder aerosols for inhalation therapy are generally produced withmean diameters primarily in the range of <5 μm. As the diameter ofparticles exceeds 3 μm, there is increasingly less phagocytosis bymacrophages. However, increasing the particle size also has been foundto minimize the probability of particles (possessing standard massdensity) entering the airways and acini due to excessive deposition inthe oropharyngeal or nasal regions.

Suitable powder compositions include, by way of illustration, powderedpreparations including the engineered EVs described herein. These can beintermixed with lactose, or other inert powders acceptable forintrabronchial administration. The powder compositions can beadministered via an aerosol dispenser or encased in a breakable capsulewhich may be inserted by the patient or clinician into a device thatpunctures the capsule and blows the powder out in a steady streamsuitable for inhalation. The compositions can include propellants,surfactants, and co-solvents and may be filled into conventional aerosolcontainers that are closed by a suitable metering valve.

Aerosols for the delivery to the respiratory tract are described, forexample, by Adjei, A. and Garren, J. Pharm. Res., 1: 565-569 (1990);Zanen, P. and Lamm, J.-W. J. Int. J. Pharm., 114: 111-115 (1995); Gonda,I. “Aerosols for delivery of therapeutic and diagnostic agents to therespiratory tract,” in Critical Reviews in Therapeutic Drug CarrierSystems, 6:273-313 (1990); Anderson et al., Am. Rev. Respir. Dis., 140:1317-1324 (1989)) and have potential for the systemic delivery ofpeptides and proteins as well (Patton and Platz, Advanced Drug DeliveryReviews, 8:179-196 (1992)); Timsina et. al., Int. J. Pharm., 101: 1-13(1995); and Tansey, I. P., Spray Technol. Market, 4:26-29 (1994);French, D. L., Edwards, D. A. and Niven, R. W., Aerosol Sci., 27:769-783 (1996); Visser, J., Powder Technology 58: 1-10 (1989)); Rudt, S.and R. H. Muller, J. Controlled Release, 22: 263-272 (1992); Tabata, Y,and Y. Ikada, Biomed. Mater. Res., 22: 837-858 (1988); Wall, D. A., DrugDelivery, 2: 10 1-20 1995); Patton, J. and Platz, R., Adv. Drug Del.Rev., 8: 179-196 (1992); Bryon, P., Adv. Drug. Del. Rev., 5: 107-132(1990); Patton, J. S., et al., Controlled Release, 28: 15 79-85 (1994);Damms, B. and Bains, W., Nature Biotechnology (1996); Niven, R. W., etal., Pharm. Res., 12(9); 1343-1349 (1995); and Kobayashi, S., et al.,Pharm. Res., 13(1): 80-83 (1996), the contents of each of which areincorporated herein by reference in their entirety.

Microemulsification technology can improve bioavailability of somelipophilic (water insoluble) pharmaceutical agents. Examples includeTrimetrine (Dordunoo, S. K., et al., Drug Development and IndustrialPharmacy, 17(12), 1685-1713, 1991 and REV 5901 (Sheen, P. C., et al., JPharm Sci 80(7), 712-714, 1991). Among other things, microemulsificationprovides enhanced bioavailability by preferentially directing absorptionto the lymphatic system instead of the circulatory system, which therebybypasses the liver, and prevents destruction of the cell-basedcompositions in the hepatobiliary circulation.

The engineered EVs described herein can be formulated with anamphiphilic carrier. Amphiphilic carriers are saturated andmonounsaturated polyethyleneglycolyzed fatty acid glycerides, such asthose obtained from fully or partially hydrogenated various vegetableoils. Such oils may advantageously consist of tri-, di-, and mono-fattyacid glycerides and di- and mono-polyethyleneglycol esters of thecorresponding fatty acids, with a particularly preferred fatty acidcomposition including capric acid 4-10, capric acid 3-9, lauric acid40-50, myristic acid 14-24, palmitic acid 4-14 and stearic acid 5-15%.Another useful class of amphiphilic carriers includes partiallyesterified sorbitan and/or sorbitol, with saturated or mono-unsaturatedfatty acids (SPAN-series) or corresponding ethoxylated analogs(TWEEN-series).

Commercially available amphiphilic carriers are particularlycontemplated, including Gelucire-series, Labrafil, Labrasol, orLauroglycol (all manufactured and distributed by Gattefosse Corporation,Saint Priest, France), PEG-mono-oleate, PEG-di-oleate, PEG-mono-laurateand di-laurate, Lecithin, Polysorbate 80, etc. (produced and distributedby a number of companies in USA and worldwide).

The engineered EV compositions provided herein can be formulated withhydrophilic polymers. Hydrophilic polymers are water-soluble, can becovalently attached to a vesicle-forming lipid, and which are toleratedin vivo without toxic effects (i.e., are biocompatible). Suitablepolymers include polyethylene glycol (PEG), polylactic (also termedpolylactide), polyglycolic acid (also termed polyglycolide), apolylactic-polyglycolic acid copolymer, and polyvinyl alcohol. Otherhydrophilic polymers which may be suitable include polyvinylpyrrolidone,polymethoxazoline, polyethyloxazoline, polyhydroxypropyl methacrylamide,polymethacrylamide, polydimethylacrylamide, and derivatized cellulosessuch as hydroxymethylcellulose or hydroxyethylcellulose.

In certain embodiments, a pharmaceutical composition as described hereincomprises a biocompatible polymer selected from the group consisting ofpolyamides, polycarbonates, polyalkylenes, polymers of acrylic andmethacrylic esters, polyvinyl polymers, polyglycolides, polysiloxanes,polyurethanes and co-polymers thereof, celluloses, polypropylene,polyethylenes, polystyrene, polymers of lactic acid and glycolic acid,polyanhydrides, poly(ortho)esters, poly(butic acid), poly(valeric acid),poly(lactide-co-caprolactone), polysaccharides, proteins, polyhyaluronicacids, polycyanoacrylates, and blends, mixtures, or copolymers thereof.

In certain embodiments, a pharmaceutical composition described herein isformulated as a liposome. Liposomes can be prepared by any of a varietyof techniques that are known in the art. See, e.g., U.S. Pat. No.4,235,871; Published PCT applications WO 96/14057; New RRC, Liposomes: Apractical approach, IRL Press, Oxford (1990), pages 33-104; Lasic D D,Liposomes from physics to applications, Elsevier Science Publishers BV,Amsterdam, 1993.

Therapeutic formulations of the engineered EV compositions as describedherein can be prepared for storage by with optional pharmaceuticallyacceptable carriers, excipients or stabilizers (Remington'sPharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the formof lyophilized formulations or aqueous solutions. Acceptable carriers,excipients, or stabilizers are nontoxic to recipients at the dosages andconcentrations employed, and include buffers such as phosphate, citrate,and other organic acids; antioxidants including ascorbic acid andmethionine; preservatives (such as octadecyldimethylbenzyl ammoniumchloride; hexamethonium chloride; benzalkonium chloride, benzethoniumchloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methylor propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; andm-cresol); low molecular weight (less than about 10 residues)polypeptides; proteins, such as serum albumin, gelatin, orimmunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone;amino acids such as glycine, glutamine, asparagine, histidine, arginine,or lysine; monosaccharides, disaccharides, and other carbohydratesincluding glucose, mannose, or dextrins; chelating agents such as EDTA;sugars such as sucrose, mannitol, trehalose or sorbitol; salt-formingcounter-ions such as sodium; metal complexes (e.g. Zn-proteincomplexes); and/or non-ionic surfactants such as TWEEN™, PLURONICS™ orpolyethylene glycol (PEG).

Vaccine or other pharmaceutical compositions comprising an engineered EVcomposition as described herein can contain a pharmaceuticallyacceptable salt, typically, e.g., sodium chloride, and preferably atabout physiological concentrations. The formulations of the vaccine orother pharmaceutical compositions described herein can contain apharmaceutically acceptable preservative. In some embodiments, thepreservative concentration ranges from 0.1 to 2.0%, typically v/v.Suitable preservatives include those known in the pharmaceutical arts.Benzyl alcohol, phenol, m-cresol, methylparaben, and propylparaben areexamples of preservatives. The formulations of the vaccine or otherpharmaceutical compositions described herein can include apharmaceutically acceptable surfactant at a concentration of 0.005 to0.02%.

Therapeutic pharmaceutical compositions described herein can alsocontain more than one active compound as necessary for the particularindication being treated, preferably those with complementary activitiesthat do not adversely affect each other.

In some embodiments in which the engineered EVs are formulated for usein or with a vaccine, the vaccine composition can be formulated with theengineered EVs as an adjuvant. In other embodiments the vaccinecomposition can be formulated with the engineered EVs and an additionaladjuvant, e.g., as known in the art.

As used herein in the context of immunization, immune response andvaccination, the term “adjuvant” refers to any substance than when usedin combination with a specific antigen produces a more robust immuneresponse than the antigen alone. When incorporated into a vaccineformulation, an adjuvant acts generally to accelerate, prolong, orenhance the quality of specific immune responses to the vaccineantigen(s). Adjuvants typically promote the accumulation and/oractivation of accessory cells or factors to enhance antigen-specificimmune responses and thereby enhance the efficacy of vaccines, i.e.,antigen-containing or encoding compositions used to induce protectiveimmunity against the antigen.

Adjuvants, in general, include adjuvants that create a depot effect,immune-stimulating adjuvants, and adjuvants that create a depot effectand stimulate the immune system. An adjuvant that creates a depot effectis an adjuvant that causes the antigen to be slowly released in thebody, thus prolonging the exposure of immune cells to the antigen. Thisclass of adjuvants includes but is not limited to alum (e.g., aluminumhydroxide, aluminum phosphate); emulsion-based formulations includingmineral oil, non-mineral oil, water-in-oil or oil-in-water-in oilemulsion, oil-in-water emulsions such as Seppic ISA series of Montanideadjuvants (e.g., Montanide ISA 720; AirLiquide, Paris, France); MF-59 (asqualene-in-water emulsion stabilized with Span 85 and Tween 80; ChironCorporation, Emeryville, Calif.); and PROVAX™ (an oil-in-water emulsioncontaining a stabilizing detergent and a micelle-forming agent; IDECPharmaceuticals Corporation, San Diego, Calif.).

An immune-stimulating adjuvant is an adjuvant that causes activation ofa cell of the immune system. It may, for instance, cause an immune cellto produce and secrete cytokines and interferons. This class ofadjuvants includes but is not limited to saponins purified from the barkof the Q. saponaria tree, such as QS21 (a glycolipid that elutes in the21st peak with HPLC fractionation; Aquila Biopharmaceuticals, Inc.,Worcester, Mass.); poly[di(carboxylatophenoxy)phosphazene (PCPP polymer;Virus Research Institute, USA); derivatives of lipopolysaccharides suchas monophosphoryl lipid A (MPL; Ribi ImmunoChem Research, Inc.,Hamilton, Mont.), muramyl dipeptide (MDP; Ribi) and threonyl-muramyldipeptide (t-MDP; Ribi); OM-174 (a glucosamine disaccharide related tolipid A; OM Pharma SA, Meyrin, Switzerland); and Leishmania elongationfactor (a purified Leishmania protein; Corixa Corporation, Seattle,Wash.). This class of adjuvants also includes CpG DNA.

Adjuvants that create a depot effect and stimulate the immune system arethose compounds which have both of the above-identified functions. Thisclass of adjuvants includes but is not limited to ISCOMS(immunostimulating complexes which contain mixed saponins, lipids andform virus-sized particles with pores that can hold antigen; CSL,Melbourne, Australia); SB-AS2 (SmithKline Beecham adjuvant system #2which is an oil-in-water emulsion containing MPL and QS21: SmithKlineBeecham Biologicals [SBB], Rixensart, Belgium); SB-AS4 (SmithKlineBeecham adjuvant system #4 which contains alum and MPL; SBB, Belgium);non-ionic block copolymers that form micelles such as CRL 1005 (thesecontain a linear chain of hydrophobic polyoxypropylene flanked by chainsof polyoxyethylene; Vaxcel, Inc., Norcross, Ga.); and Syntex AdjuvantFormulation (SAF, an oil-in-water emulsion containing Tween 80 and anonionic block copolymer; Syntex Chemicals, Inc., Boulder, Colo.).

The active ingredients of the pharmaceutical compositions describedherein can also be entrapped in microcapsules prepared, for example, bycoacervation techniques or by interfacial polymerization, for example,hydroxymethylcellulose or gelatin-microcapsules andpoly-(methylmethacylate) microcapsules, respectively, in colloidal drugdelivery systems (for example, liposomes, albumin microspheres,microemulsions, nano-particles and nanocapsules) or in macroemulsions.Such techniques are disclosed in Remington's Pharmaceutical Sciences16th edition, Osol, A. Ed. (1980).

In some embodiments, sustained-release preparations can be used.Suitable examples of sustained-release preparations includesemipermeable matrices of solid hydrophobic polymers containing acomposition described herein in which the matrices are in the form ofshaped articles, e.g., films, or microcapsule. Examples ofsustained-release matrices include polyesters, hydrogels (for example,poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides(U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and yethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradablelactic acid-glycolic acid copolymers such as the LUPRON DEPOT™(injectable microspheres composed of lactic acid-glycolic acid copolymerand leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid. Whilepolymers such as ethylene-vinyl acetate and lactic acid-glycolic acidenable release of molecules for over 100 days, certain hydrogels releaseproteins for shorter time periods. When encapsulated, the compositioncan remain in the body for a long time (e.g., up to about 1 hour,between 1-12 hours, 12-24 hours, 24 hours to 2 days, 2-3 days, 3-4 days,4-5 days, 5-6 days, 6-7 days, 1-2 weeks, 3-4 weeks, 4 weeks to 2 months,2-3 months, 3-4 months, 4-5 months, 5-6 months, or more than 6 months,or a variation thereof), denature, or aggregate as a result of exposureto moisture at 37° C., resulting in a loss of biological activity andpossible changes in immunogenicity. Rational strategies can be devisedfor stabilization depending on the mechanism involved. For example, ifthe aggregation mechanism is discovered to be intermolecular S—S— bondformation through thio-disulfide interchange, stabilization can beachieved by modifying sulfhydryl residues, lyophilizing from acidicsolutions, controlling moisture content, using appropriate additives,and developing specific polymer matrix compositions.

Administration, Dosing, Efficacy

The engineered EV compositions, pharmaceutical compositions, or vaccinecompositions described herein can be formulated, dosed, and administeredin a fashion consistent with good medical practice. Factors forconsideration in this context include the particular disorder beingtreated, the particular subject being treated, the clinical condition ofthe individual subject, the cause of the disorder, the site of deliveryof the vaccine composition, the method of administration, the schedulingof administration, and other factors known to medical practitioners.

Generally, application of artificial synapses as therapy will take intoaccount similar parameters as other therapeutic strategies, includingconcentration, timing of delivery, and sustained bioavailability atinjury/disease site. Extracellular vesicle can be delivered via a numberof routes: intravenous, intracoronary, and intramyocardial.Extracellular vesicles (e.g., exosomes), also allow for new deliveryroutes that were previously infeasible for cell therapy, such asinhalation or injection. These various approaches are described below,including injection, topical application, enteral administration, andpulmonary delivery.

The engineered EV compositions provided herein can be administered to asubject in need thereof by any appropriate route which results in aneffective treatment in the subject. As used herein, the terms“administering,” and “introducing” are used interchangeably and refer tothe placement of a composition provided herein into a subject by amethod or route which results in at least partial localization of suchcompositions at a desired site, such as a site of inflammation or atumor, such that a desired effect(s) is produced. The compositions canbe administered to a subject by any mode of administration that deliversthe composition systemically or to a desired surface or target, and caninclude, but is not limited to, injection, infusion, instillation, andinhalation administration. To the extent that the composition can beprotected from inactivation in the gut, oral administration forms arealso contemplated. “Injection” includes, without limitation,intravenous, intramuscular, intra-arterial, intrathecal,intraventricular, intracapsular, intraorbital, retro-orbital,intravitreal, intraocular, intracardiac, intradermal, intraperitoneal,transtracheal, subcutaneous, subcuticular, intraarticular, sub capsular,subarachnoid, intraspinal, intracerebral, intratarsal, and intrasternal,intratumoral injection, and infusion or the like as known in the art.

A therapeutic does of the present invention may be delivered to apatient by means of controlled release, for example but not limited to,implantable pump and implantable cannulas to provide continuous accessto the venous or arterial system.

Topical application refers to applying or spreading a composition of thepresent invention onto surfaces on or in the body, both internallyand/or externally, in a therapeutically effective amount for localand/or systemic treatment. Topical application may be epicutaneuoswherein a composition of the present invention may be directly appliedonto a localized surface of the skin or mucous membranes. Topicalapplication may include transdermal application wherein a composition ofthe present invention may be absorbed into the body to obtain systemicdelivery and systemic distribution. Topical application formulations mayinclude, but are not limited to, creams, foams, gels, lotions,solutions, ointments, dermal patch, transdermal patches, powder, solid,sponge, tape, vapor, paste, film, liposomes, balm, shampoo, spray, ortincture or the like or a combination thereof. A therapeutic dose of acomposition of the present invention may be delivered vaginally (forexample a vaginal suppository, vaginal ring, douche, intrauterinedevice, intravesical infusion, and the like) or urethra or the like or acombination thereof.

Enteral administration refers to a composition of the present inventionadministered via the gastrointestinal tract in a therapeuticallyeffective amount for local or systemic treatment. Enteral administrationmay include, but is not limited to, delivery of a composition of thepresent invention via the mouth, sublingual, esophagus, gastric (forexample the stomach), small intestines, large intestines or rectum. Oraldelivery of the present invention may include, but is not limited to,the use of a capsule, pastille, pill, tablet, solution, gel, suspension,emulsion, syrup, elixir, tincture, mouthwash, lozenges, chewing gum,lollipop, cream, foam, solution, powder, solid, vapor, liposomes, spray,or tincture osmotic-controlled release oral delivery system, or thelike. Gastric delivery may involve the use of a tube or nasal passagethat leads directly to the stomach, for example, a percutaneousendoscopic gastrostomy tube. Gastric delivery may involve directinjection made through the abdominal wall. Rectal delivery may involve,but is not limited to, the use of a suppository, ointment, enema, murphydrip, or the like. A therapeutic does of the present invention may bedelivered to a patient by means of controlled release, for example butnot limited to, controlled release drug delivery pellet or pill.

Inhalation (i.e., pulmonary delivery, pulmonary administration refers todelivery to the respiratory system through the respiratory route,including but not limited to, intranasal administration, oraladministration, and oral inhalative administration (e.g. intratrachealinstillation and intratracheal inhalation) of a therapeuticallyeffective amount for local or systemic treatment. Pulmonary delivery ofa therapeutically effective amount of a composition of the presentinvention may be achieved by dispersion, for example by using a syringe.Pulmonary delivery of a composition of the present invention may beachieved by aerosol administration, wherein aerosol administration maydeposit a therapeutically effective amount of the present invention bygravitational sedimentation, inertial impaction, or diffusion.

Intravenous delivery technique can occur through a peripheral or centralvenous catheter. As the simplest delivery mode, this technique avoidsthe risk of an invasive procedure. However, intravenous may be regardedas a comparatively inefficient and less localized delivery method, as ahigh percentage of infused cell exosomes may become sequestered inorgans such as the lung, liver, or spleen. Such sequestration may resultin few or no cellular exosomes reaching broader circulation or haveunintended systemic effects following their distribution.

In certain embodiments, administration can include delivery to a tissueor organ site that is the same as the site of diseased and/ordysfunctional tissue. In certain embodiments, administration can includedelivery to a tissue or organ site that is different from the site ordiseased and/or dysfunctional tissue. In certain embodiments, thedelivery is via inhalation or oral administration. In variousembodiments, administration of artificial synapses can includecombinations of multiple delivery techniques.

In some embodiments, the compositions described herein are administeredby aerosol administration, nebulizer administration, or tracheal lavageadministration.

The term “effective amount” as used herein refers to the amount of anengineered EV composition needed to alleviate or prevent at least one ormore symptom of a disease or disorder (e.g., autoimmune disease orcancer), and relates to a sufficient amount of pharmacologicalcomposition to provide the desired effect, e.g., reduce the pathology,or any symptom associated with or caused by the a disease. The term“therapeutically effective amount” therefore refers to an amount of anengineered EV composition or vaccine composition described herein usingthe methods as disclosed herein, that is sufficient to affect aparticular disease state when administered to a typical subject. Aneffective amount as used herein would also include an amount sufficientto delay the development of a symptom of the disease, alter the courseof a symptom disease (for example, but not limited to, slow theprogression of a symptom of the disease), or reverse a symptom of thedisease. Thus, it is not possible to specify the exact “effectiveamount.” However, for any given case, an appropriate “effective amount”can be determined by one of ordinary skill in the art using only routineexperimentation.

Effective amounts, toxicity, and therapeutic efficacy can be determinedby standard pharmaceutical procedures in cell cultures or experimentalanimals, e.g., for determining the LD50 (the dose lethal to 50% of thepopulation) and the ED50 (the dose therapeutically effective in 50% ofthe population). The dosage can vary depending upon the dosage formemployed and the route of administration utilized. The dose ratiobetween toxic and therapeutic effects is the therapeutic index and canbe expressed as the ratio LD50/ED50. Compositions and methods thatexhibit large therapeutic indices are preferred. A therapeuticallyeffective dose can be estimated initially from cell culture assays.Also, a dose can be formulated in animal models to achieve a circulatingplasma concentration range that includes the IC50 (i.e., theconcentration of the engineered EVs or fusion polypeptides providedherein), which achieves a half-maximal inhibition of symptoms) asdetermined in cell culture, or in an appropriate animal model. Levels oftherapeutic engineered EVs in plasma can be measured, for example, byhigh performance liquid chromatography, enzyme linked immunosorbentassay (ELISA), flow cytometry, FACS sorting, western blot, massspectroscopy, tunable resistive pulse sensing, ExoView®, qRT-PCR, nextgeneration sequencing (NGS), or by any analysis technique known by oneof ordinary skill in the art. The effects of any particular dosage canbe monitored by a suitable bioassay. The dosage can be determined by aphysician and adjusted, as necessary, to suit observed effects of thetreatment.

The engineered EV compositions, pharmaceutical compositions, or vaccinecompositions described herein can be formulated, in some embodiments,with one or more additional therapeutic agents currently used to preventor treat the infection, for example. The effective amount of such otheragents depends on the amount of an engineered EV in the formulation, thetype of disorder or treatment, and other factors discussed above. Theseare generally used in the same dosages and with administration routes asused herein before or about from 1 to 99% of the heretofore employeddosages.

The dosage ranges for the pharmaceutical compositions described hereindepend upon the potency and encompass amounts large enough to producethe desired effect. The dosage should not be so large as to causeunacceptable adverse side effects. Generally, the dosage will vary withthe age, condition, health, and sex of the patient and can be determinedby one of skill in the art. The dosage can also be adjusted by theindividual physician in the event of any complication. In someembodiments, the dosage ranges from 0.001 mg/kg body weight to 100 mg/kgbody weight. In some embodiments, the dose range is from 5 μg/kg bodyweight to 100 μg/kg body weight. Alternatively, the dose range can betitrated to maintain serum levels between 0.1 μg/mL and 1000 μg/mL. Forsystemic administration, subjects can be administered a therapeuticamount, such as, e.g., 0.1 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 2.5mg/kg, 5 mg/kg, 7.5 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30mg/kg, 40 mg/kg, 50 mg/kg, or more. These doses can be administered byone or more separate administrations, or by continuous infusion. Forrepeated administrations over several days or longer, depending on thecondition, the treatment is sustained until, for example, the infectionis treated, as measured by the methods described above or known in theart. However, other dosage regimens can be useful.

In various embodiments, the quantities of artificial synapses that areadministered to achieve these effects range from 1×10⁶ to 1×10, 1×10⁷ to1×10⁸, 1×10⁸ to 1×10⁹, 1×10⁹ to 1×10¹⁰, 1×10¹⁰ to 1×10¹¹, 1×10¹¹ to1×10¹², 1×10¹² to 1×10¹³, 1×10¹³ to 1×10¹⁴, 1×10¹⁴ to 1×10¹⁵, 1×10¹⁵ ormore EVs/artificial synapses. In other embodiments, the numbers ofartificial synapses are relative to the number of cells used in aclinically relevant dose for a cell-therapy method. For example,defining an effective dose range, dosing regimen and route ofadministration, may be guided by studies using fluorescently labeledartificial synapses, and measuring target tissue retention, which canbe >10×, >50×, or >100× background, as measured 5, 10, 15, 30, or 30 ormore min as a screening criterion. In certain embodiments, >100×background measured at 30 mins is a baseline measurement for a low andhigh dose that is then assess for safety and bioactivity (e.g., usingMRI endpoints: scar size, global and regional function of the targetorgan being treated). In various embodiments, single doses are comparedto two, three, four, four or more sequentially-applied doses. In variousembodiments, the repeated or sequentially-applied doses are provided fortreatment of an acute disease and/or condition. In various embodiments,the repeated or sequentially-applied doses are provided for treatment ofa chronic disease and/or condition. In other embodiments, administrationof the plurality of artificial synapses is adjunctive to standardtherapy.

In other embodiments, administering a composition includes 1×10¹⁰ ormore artificial synapses in a single dose. In various embodiments,exosome quantity may be defined by protein quantity, such as dosagesincluding 1-10, 10-25, 25-50, 50-75, 75-100, or 100 or more mg exosomeprotein. In other embodiments, a single dose is administered multipletimes to the subject. In other embodiments, administering a compositionconsists of one or more of: injection, topical administration, enteral,intravenous, intra-arterial, or inhalation.

In various embodiments, exosome quantity may be defined by proteinquantity, such as dosages including 1-10, 10-25, 25-50, 50-75, 75-100,or 100 or more mg exosome protein. In various embodiments, administeringa composition includes multiple dosages of the artificial synapses. Invarious embodiments, the repeated or sequentially-applied doses areprovided for treatment of an acute disease and/or condition. In variousembodiments, the repeated or sequentially-applied doses are provided fortreatment of a chronic disease and/or condition.

In other embodiments, administering a composition including a pluralityof artificial synapses to the subject is adjunctive to standard therapy.

The duration of a therapy using the methods described herein willcontinue for as long as medically indicated or until a desiredtherapeutic effect (e.g., those described herein) is achieved. Incertain embodiments, the administration of the vaccine compositiondescribed herein is continued for 1 month, 2 months, 4 months, 6 months,8 months, 10 months, 1 year, 2 years, 3 years, 4 years, 5 years, 10years, 20 years, or for a period of years up to the lifetime of thesubject.

As will be appreciated by one of skill in the art, appropriate dosingregimens for a given composition can comprise a singleadministration/immunization or multiple ones. Subsequent doses may begiven repeatedly at time periods, for example, about two weeks orgreater up through the entirety of a subject's life, e.g., to provide asustained preventative effect. Subsequent doses can be spaced, forexample, about two weeks, about three weeks, about four weeks, about onemonth, about two months, about three months, about four months, aboutfive months, about six months, about seven months, about eight months,about nine months, about ten months, about eleven months, or about oneyear after a primary immunization.

The precise dose to be employed in the formulation will also depend onthe route of administration and should be decided according to thejudgment of the practitioner and each patient's circumstances.Ultimately, the practitioner or physician will decide the amount of theengineered EV or composition thereof to administer to particularsubjects.

Methods of Modulating Inflammation and Treating Autoimmune Diseases

The artificial synapses/engineered EVs and compositions thereof providedherein can be deployed in a therapeutic strategy against virtually anyinjury/disease, as providing a platform for altering biologicalsignaling. This includes, for example, inflammation and immunesignaling, which plays a role in virtually all injuries and diseases inliving organisms.

Thus, described herein is a method of modulating inflammation, includingselecting a subject afflicted with an inflammatory related diseaseand/or condition; and administering to the subject a compositionincluding a plurality of artificial synapses (engineered EVs) to thesubject, wherein administration of the composition modulatesinflammation.

As used herein, the term “inflammation” or “inflamed” refers toactivation or recruitment of the immune system or immune cells (e.g. Tcells, B cells, macrophages). A tissue that has inflammation can becomereddened, white, swollen, hot, painful, sensitivity, exhibit a loss offunction, or have a film or mucus. Methods of identifying inflammationare well known in the art. Inflammation typically occurs followinginjury, infection by a microorganism, exposure to a substance (e.g., atoxin, chemical, or dust) or autoimmune dysfunction. Onset ofinflammation may be rapid (e.g., immediately following injury) or slow(e.g., repeated exposure to an irritant such as a chemical over time)with a duration of minutes, hours, days, months, years, or anindividual's life.

Inflammation plays a vital role in alerting the immune system ofpotential danger and damage within a body. Inflammation is necessary tocontrol and repair injury. For example, acute inflammation is a responseto physical trauma, infection, and stress. Acute inflammation helpsprevent further injury and triggers healing and recovery. Unfortunately,inflammation can become excessive and inappropriately active, lastingbeyond the typical recovery time from an injury or infection. Whereinhealthy inflammation helps a body respond to injury, chronicinflammation perpetuates injury and may lead to negative consequences toone's health. In particular, autoimmune diseases are chronic diseasesfrom a host's immune system attacking itself, often due to aberrantbiological signaling in the host. Restoring normal homeostatic signalingvia application of artificial synapses, particularly targeting immunecheckpoints, represents a highly promising avenue. For example, surfacebound immune-checkpoint proteins or fragments thereof may modulateimmune cell stimulation and affect suppression of immune cell functionwhen delivered via artificial synapses. Injection, inhalation, ingestionor topical application of artificial synapses with surface boundimmune-checkpoint proteins or fragments thereof may be used to treatimmune, auto-immune, inflammatory, and auto-inflammatory conditions.Examples include chronic obstructive pulmonary disease (COPD) which isan inflammatory, progressive, life-threatening lung disease, psoriasis,a common chronic noncommunicable inflammatory skin disease, arthritis, adebilitating and painful degeneration of joints, among otherswell-understood to one of skill in the art.

In other embodiments, the inflammatory related disease and/or conditionis acute, for example septicemia. In other embodiments, the inflammatoryrelated disease and/or condition is chronic, for example chronicobstructive pulmonary disease. In other embodiments, the inflammatorycondition is an autoimmune disease wherein the autoimmune disease and/orcondition is one or more of: polymyositis, dermatomyositis, Graves'disease, Hashimoto's thyroiditis, myasthenia gravis, vasculitis,multiple sclerosis, psoriasis, rheumatoid arthritis, psoriaticarthritis, scleroderma, systemic lupus erythematosus, inflammatory boweldisease, Crohn's disease, hyperthyroidism, autoimmune adrenalinsufficiency, Sjogren syndrome, type I diabetes mellitus, autoimmunehemolytic anemia, idiopathic thrombocytopenic purpura, myastheniagravis, ulcerative colitis, uveitis, polyarteritis nodosa, relapsingpolychondritis, Behcet's disease, reactive arthritis, ankylosingspondylitis, Guillain-Barre syndrome, or optic neuropathy. In otherembodiments, the disease and/or condition is chronic obstructivepulmonary disease, rheumatoid arthritis, uveoretinitis, psoriasis, andeczema. In other embodiments, the disease and/or condition is irritablebowel disease, multiple sclerosis or lupus

In other embodiments, the inflammatory related disease and/or conditionis an ocular disease. As used herein, the terms “ocular disease”, “eyedisorder” and “eye disease” are used interchangeably and refer to adisease or disorder that affects the health and/or vision of either oneor both eyes or the general area of the eye(s), eye lid(s), or areasurrounding or in near proximity to the eye(s). Eye disease may include,but are not limited to, macular degeneration (e.g., age-related maculardegeneration), cataracts, diabetic retinopathy, diabetic macular edema,eye floaters, eye flashes, glaucoma, amblyopia, strabismus, retinitis(e.g., CMV retinitis), color blindness, keratoconus, retinal detachment,eyelid twitching, ocular hypertension, blepharitis, uveitis, Bietti'scrystalline dystrophy, blepharospasm, cornea and corneal diseases, dryeye, histoplasmosis, macular hole, macular pucker, conjunctivitis,presbyopia, retinoblastoma, retinitis pigmentosa, retinopathy, Stargardtdisease, Usher syndrome, uveal Coloma, and vitreous detachment, or thelike.

Described herein is a method for treatment including, selecting asubject in need of treatment, administering a composition including aplurality of artificial synapses to the individual, whereinadministration of the composition treats the subject. In certainembodiments, the subject is in need to treatment for a disease and/orcondition involving tissue damage or dysfunction.

Described herein is a method of treating an autoimmune disease,inflammation, inflammatory disease or condition, or cancer in a subject,the method comprising: administering to a subject the an engineered EVor composition thereof as provided herein to the subject.

Measured or measurable parameters include clinically detectable markersof disease, for example, elevated or depressed levels of a clinical orbiological marker, as well as parameters related to a clinicallyaccepted scale of symptoms or markers for a disease or disorder. It willbe understood, however, that the total usage of the compositions andformulations as disclosed herein will be decided by the attendingphysician within the scope of sound medical judgment. The exact amountrequired will vary depending on factors such as the type of diseasebeing treated.

Non-limiting examples of clinical tests that can be used to assessautoimmune diseases, inflammatory conditions, or inflammation parametersinclude blood tests, skin biopsy, MRI, eye examination, ocular pressuretests, etc. Where necessary or desired, animal models of injury ordisease can be used to gauge the effectiveness of a particularcomposition as described herein. For example, an EAU animal model, asdemonstrated in the working examples can be used.

In various embodiments, administration of the plurality of artificialsynapses alters gene expression in the damaged or dysfunctional tissue,improves viability of the damaged tissue, and/or enhances regenerationor production of new tissue in the individual. In various embodiments,administration of the plurality of artificial synapses alters geneexpression in the damaged or dysfunctional tissue, improves viability ofthe damaged tissue, and/or enhances regeneration or production of newtissue in the individual.

In various embodiments, the damaged or dysfunctional tissue is in needof repair, regeneration, or improved function due to an acute event.Acute events include, but are not limited to, trauma such as laceration,crush or impact injury, shock, loss of blood or oxygen flow, infection,chemical or heat exposure, poison or venom exposure, drug overuse oroverexposure, and the like. Other sources of damage also include, butare not limited to, injury, age-related degeneration, cancer, andinfection. In several embodiments, the regenerative cells used toprepare the engineered EVs provided herein are from the same tissue typeas is in need of repair or regeneration. In several other embodiments,the regenerative cells are from a tissue type other than the tissue inneed of repair or regeneration. In some embodiments, the engineered EVsprovided herein are derived from the subject being treated. In someembodiments, the engineered EVs are derived from a donor subject.

In other embodiments, the damaged or dysfunctional tissue is in need ofrepair, regeneration, or improved function due to damage from chronicdisease.

Some Selected Definitions

All references cited herein are incorporated by reference in theirentirety as though fully set forth. Unless defined otherwise, technicaland scientific terms used herein have the same meaning as commonlyunderstood by one of ordinary skill in the art to which this inventionbelongs. Allen et al., Remington: The Science and Practice of Pharmacy22^(nd) ed., Pharmaceutical Press (Sep. 15, 2012); Hornyak et al.,Introduction to Nanoscience and Nanotechnology, CRC Press (2008);Singleton and Sainsbury, Dictionary of Microbiology and MolecularBiology 3^(rd) ed., revised ed., J. Wiley & Sons (New York, N.Y. 2006);Smith, March's Advanced Organic Chemistry Reactions, Mechanisms andStructure 7^(th) ed., J. Wiley & Sons (New York, N.Y. 2013); Singleton,Dictionary of DNA and Genome Technology 3^(rd) ed., Wiley-Blackwell(Nov. 28, 2012); and. Green and Sambrook, Molecular Cloning: ALaboratory Manual 4th ed., Cold Spring Harbor Laboratory Press (ColdSpring Harbor, N.Y. 2012), provide one skilled in the art with a generalguide to many of the terms used in the present application. Forreferences on the preparation and structure of antibodies and fusionpolypeptides, see, e.g., Greenfield, Antibodies A Laboratory Manual2^(nd) ed., Cold Spring Harbor Press (Cold Spring Harbor N.Y., 2013);Köhler and Milstein, Derivation of specific antibody-producing tissueculture and tumor lines by cell fusion, Eur. J. Immunol. 1976 July,6(7):511-9; Queen and Selick, Humanized immunoglobulins, U.S. Pat. No.5,585,089 (1996 December); and Riechmann et al., Reshaping humanantibodies for therapy, Nature 1988 Mar. 24, 332(6162):323-7. See also,Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed.Public Health Service, National Institutes of Health, Bethesda, Md.(1991), Lanzavecchia et al., Eur. J. Immunol. 17, 105 (1987)), Huston etal., Proc. Natl. Acad. Sci. U.S.A., 85, 5879-5883 (1988), Bird et al.,Science 242, 423-426 (1988), Brinkman et al. mAbs Vol 9, No. 2, 182-212(2017), Chothia & Lesk, J. Mol. Biol, 196:901-917 (1987), Chothia etal., Nature 342:877-883 (1989)), Holliger et al. (1993) Proc. Natl.Acad. Sci. USA 90: 6444-6448; Poljak (1994) Structure 2: 1121-1123);Kontermann and Dubel eds., Antibody Engineering, Springer-Verlag, N.Y.(2001), p. 790 (ISBN 3-540-41354-5, Zapata et al. (1995) Protein Eng.8(10): 1057-1062; Morrison, et al., Proc. Natl. Acad. Sci. USA, 81:6851(1984), U.S. Pat. Nos. 4,816,567, 5,693,780, which are incorporatedherein by reference in their entireties.

One skilled in the art will recognize many methods and materials similaror equivalent to those described herein, which could be used in thepractice of the present invention. Indeed, the present invention is inno way limited to the methods and materials described. For purposes ofthe present invention, the following terms are defined below.

As used herein, the term “extracellular vesicle” and “vesicle” are usedinterchangeably and refer to a particle, wherein the particle comprisesa phospholipid bilayer that encloses an internal space and an exteriorsurface and may or may not be derived from a cell. The size ofextracellular vesicles can range between 20 nm to 3 μm in diameter butmay be smaller than 20 nm or larger than 3 μm. Examples of extracellularvesicles include, but is not limited to, exosomes (for example smallexosomes and large exosomes), ectosomes, macrovesicles, microparticles,apoptotic bodies, vesicular organelles, oncosomes (for examples largeoncosomes), exospheres, exomeres, cell derived nanovesicles (CDN) (e.g.,by genesis via grating or shearing cells), liposomes or the like knownby one of ordinary skill in the art. Extracellular vesicles mayoriginate naturally via known or unknown biosynthetic pathways.Extracellular vesicles may be promoted to originate by using mechanicalmethods such as cell grating or cell shearing wherein a cell is gratedor sheared causing portions or parts of the cell membrane to fromvesicles. For example, CDNs may be formed by using mechanical methodssuch as cell grating or cell shearing wherein a cell is grated orsheared causing portions or parts of the cell membrane to from vesicles.Additional non-limiting examples of mechanical methods that can be usedto form cell derived nanovesicles are further described in detail, e.g.,Goh, W. J., Zou, S., Ong, W. Y. et al. Bioinspired Cell-DerivedNanovesicles versus Exosomes as Drug Delivery Systems: a Cost-EffectiveAlternative. Sci Rep 7, 14322 (2017).https://doi.org/10.1038/s41598-017-14725-x, the contents of which areincorporated herein by reference in their entireties.

Extracellular vesicles comprise cargo, wherein the term “cargo” refersto peptides, proteins, nucleic acids, lipids, metabolites,carbohydrates, biomolecules, small molecules, large molecules, vesicles,organelles, or fragments thereof. In some embodiments, cargo may referto existing drugs or therapeutics known in the art. Extracellularvesicle cargo may be located within the internal space of theextracellular vesicle. Extracellular vesicle cargo may be membrane boundand span one or both layers of the extracellular vesicle phospholipidbilayer (for example a transmembrane protein). Extracellular vesiclecargo may be in contact with the external or internal surface of theextracellular vesicle, for example through a covalent bond or anon-covalent bond. The phospholipid bilayer of the extracellular vesiclemay comprise one or more transmembrane proteins, wherein a portion ofthe one or more transmembrane membrane proteins is located within theinternal space of the extracellular vesicle. The phospholipid bilayer ofthe extracellular vesicle may comprise one or more transmembraneproteins, wherein the one or more transmembrane membrane proteinscomprises a domain on the exterior of the extracellular vesicle. Thephospholipid bilayer of the extracellular vesicle may comprise one ormore transmembrane proteins, wherein the one or more transmembranemembrane proteins comprises a domain on the interior of theextracellular vesicle. Cargo may refer to a protein on the luminal side(e.g., in the internal space) of the extracellular vesicle wherein saidprotein encodes a vesicle targeting domain that may be in contact withthe interior phospholipid layer of the extracellular vesicle. Cargo mayrefer to a protein on the luminal side (e.g., in the internal space) ofthe extracellular vesicle wherein said protein encodes a vesicletargeting domain that may be in contact with the interior phospholipidlayer of the extracellular vesicle and wherein said protein may bepresented into the internal space of the extracellular vesicle.

As used herein, the terms “sticky binder” and “vesicle targeting domain”and “anchor protein” are used interchangeably and refer to a proteinthat is covalently or non-covalently attached to at least one lipidwherein the one or more lipid is embedded within a membrane (e.g. a cellmembrane), and the lipid serves to anchor the protein to the membrane.The terms “sticky binder” and “vesicle targeting domain” and “anchorprotein” can also mean a protein sequence that encodes for one or moretransmembrane domains wherein the one or more transmembrane domainsspans at least partly through a phospholipid bilayer, for example thephospholipid bilayer of an extracellular vesicle. The transmembranedomain can be of a Type I or Type II membrane protein. Transmembranedomains can be structurally identified using methods known to those ofskill in the art, such as sequence analysis programs that identifyhydrophobic and hydrophilic domains (for example TMHMM Server, v.2.0—DTU, Erik L. L. Sonnhammer, Gunnar von Heijne, and Anders Krogh: Ahidden Markov model for predicting transmembrane helices in proteinsequences. In Proc. of Sixth Int. Conf. on Intelligent Systems forMolecular Biology, p 175-182 Ed J. Glasgow, T. Littlejohn, F. Major, R.Lathrop, D. Sankoff, and C. Sensen Menlo Park, Calif.: AAAI Press, 1998,which is incorporated herein by reference in its entirety.)

A vesicle targeting domain may include, but is not limited to, one ormore prenylation site, fatty acylation site, and/orglycosylphosphatidylinositol (GPI) linked protein. One preferredembodiment of a vesicle targeting domain is the GPI sequence from CD55.Another preferred embodiment of a vesicle targeting domain is the GPIsequence from CD59. Another embodiment of a vesicle targeting domain isthe C1C2 domain from MFGE8. Other embodiments of sequences for vesicletargeting domains include transmembrane regions of CD9 (for exampletransmembrane 2 or 3 of CD9, CD9tm2 or CD9tm3, respectively), K-Ras (forexample K-Ras4A and K-Ras4B), transmembrane domain from A Disintegrinand Metalloproteinase Domain-containing protein 10 (ADAM10, also knownas CDw156 or CD156c) or other ADAM proteins. Vesicle targeting domainsmay include one or more sequences from 4F2 (for example 4F2 encoded bythe solute carrier family 3 member 2 (SLC3A2) gene which makes up theheavy subunit of CD98). Vesicle targeting domains can include a sequencefor one or more myristoylation sites. For example, the protein sequencefor a myristoylation site from myristoylated alanine-rich C-kinasesubstrate (MARCKS) protein. Vesicle targeting domains can include asequence for one or more palmitoylation sites. For example, themyristoylation sequence from the MARCKS protein may be modified toencode for a palmitoylation site. All variants, isoforms, or fragmentsor the like known by one of ordinary skill in the art are encompassed bythe present invention.

Vesicle targeting domains may include transmembrane sequences from Homosapiens transferrin receptor 2 (TFR2), transcript variant 1 (transferrinreceptor protein 2 isoform 1) or versions therefore. In a preferredembodiment, the vesicle targeting domain may be a transmembrane domainfrom CD298.

As used herein, the terms “proteins” and “peptides” and “polypeptides”are used interchangeably herein to designate a series of amino acidresidues connected to the other by peptide bonds between the alpha-aminoand carboxy groups of adjacent residues. Although “protein” is oftenused in reference to relatively large polypeptides, and “peptide” isoften used in reference to small polypeptides, usage of these terms inthe art overlaps and varies. The term “peptide” as used herein refers topeptides, polypeptides, proteins and fragments of proteins, unlessotherwise noted. The terms “protein” and “peptide” are usedinterchangeably herein when referring to a gene product and fragmentsthereof. Thus, exemplary peptides or proteins include gene products,naturally occurring proteins, homologs, orthologs, paralogs, fragmentsand other equivalents, variants, fragments, and analogs of theforegoing.

“As used herein, the term “linker” refers to a synthetic proteinsequence of amino acids that is used to connect two polypeptide domainsvia peptide bonds.

As used herein, the term “fusion protein” refers to a single chimericprotein comprising a protein of interest (e.g. checkpoint protein)joined to an exogenous protein or protein fragment (e.g. an anchorprotein), wherein the components of the fusion protein are linked toeach other by peptide-bonds, either directly or through a peptidelinker. The anchor protein of the fusion protein may enhanceincorporation of the fusion protein onto and/or into the membrane of avesicle, for example the internal and/or external leaflet of thephospholipid bilayer of an exosome membrane. The fusion protein may haveat least a part of an amino acid sequence of an immune checkpointprotein or proteins involved in immune synapses. The fusion protein mayhave at least a part of an amino acid sequence of A2AR, VTCN1, Galectin9, FGL-1, PECAM-1, TSG-6, STAB-1, NRP1, NRP2, SEMA3A, SEMA3F, RGMB,TIM-3, TIGIT, HLA class I, HLA class II, VISTA, HMGB1,phosphatidylserine, T-cell receptor (TCR), SHP-1, SHP-2, FBXO38, SH2D1A,B7RP1, IDO, NOX2, TNFRSF18, B7-H4, B7-H5, SISP1, B7-H6, B7-H7, APLNR,IFN y, PD-1, WNT5A, IL-6, IL-10, NKG2 family of C-type lectin receptors,ligands of NKG2 family, killer cell immunoglobulin-like receptors, CD2,CD4, CD8, CD27, CD27 ligand (CD70), CD28, CD28H, CD39, CD40, CD44, CD47,CD63, CD66a, CD80, B7-2, CD86, CD73, CD94, CD96, CD101, CD112, CD112R,CD122, CD134, CD137 (4-1BB), CD137 ligand (4-1BBL), CD152, CD154, CD155,CD158, CD158a, CD158g, CD158h, KIR2DL1, KIR2DS1, KIRDS3, KIR2DS5, CD160,CD172a, CD200, CD200R, CD223, CD226, CD252, CD270, CD272, CD273, CD274,CD275, CD276, CD278, CD279 (PD-1), CD279 ligand (PD-L1/PDL-2), CD328,CD329, and/or CD337. The fusion protein may have a polypeptide linkersequence (e.g., an Fc domain and/or a GSSG linker), followed by an aminoacid sequence coding for an anchor protein sequence (e.g., a prenylationsite, fatty acylation site, or a GPI sequence) or any isoform, fragment,variation thereof, or a ligand to the aforementioned proteins thereof,or the like known by one of ordinary skill in the art. All variants areencompassed by the present invention.

As used herein, the term “immune synapse” and “cell synapse” are usedinterchangeably and refer to cell-to-cell interaction wherein saidinteraction results in activation, suppression, and/or adhesion ofeither one or more cells. Immune synapse or cell synapse are mediated byproteins that may be cytoplasmic, membrane bound, membrane associated,and/or secreted. Immune or cell synapses may be mediated by one or more“immune checkpoint proteins” which herein refers to any protein that isinvolved in maintaining immune homeostasis or plays a role in regulatingimmune activation or suppression. Immune checkpoint proteins may becytoplasmic, membrane bound, membrane associated, and/or secreted.

As used herein, the term “fragment” or “active fragment” refers to aportion of a nucleic acid or polypeptide provided herein that retainsthe ability to be expressed by the engineered EVs provided herein. Insome embodiments, the active fragment retains the ability to activate atarget polypeptide, thereby increasing the activity of said targetpolypeptide (e.g., suppressing an immune response).

As used herein, the terms “specifically bind” and/or “specificallyrecognize” or “substantially binds” refers to the affinity of a bindingmolecule for a target molecule compared to the binding molecule'saffinity for non-target molecules. A binding molecule (e.g., a POIdomain) that specifically binds a target molecule (e.g., a targetpolypeptide provided herein) does not substantially recognize or bindnon-target molecules. e.g., an antibody “specifically binds” and/or“specifically recognize” another molecule, meaning that this interactionis dependent on the presence of the binding specificity of the moleculestructure, e.g., an antigenic epitope. As used herein, “non-specificbinding” and “background binding” refers to the interaction that doesnot depend on the presence of specific structure (e.g., a specificantigenic epitopes). Methods of measuring binding of a polypeptide to atarget are known in the art (e.g., differential scanning calorimetry,isothermal titration calorimetry, spectroscopy, crystallography, surfaceplasmon resonance, co-immunoprecipitation, pulldown assays,crosslinking, yeast two-hybrid system, tandem affinity purification-massspectroscopy, protein microarrays, bio-layer interferometry, far-Westernblots, computational prediction, analytical ultracentrifugation, lightscattering, fluorescence spectroscopy, resonance energy transfer, ELISAor ELISPOT assays, or any other assays known in the art).

As used herein, the terms “treat,” “treatment,” “treating,” or“amelioration” refer to therapeutic treatments, wherein the object is toreverse, alleviate, ameliorate, inhibit, slow down or stop theprogression or severity of a condition associated with, a disease ordisorder. The term “treating” includes reducing or alleviating at leastone adverse effect or symptom of a condition, disease or disorderassociated with an infection or a cancer. Treatment is generally“effective” if one or more symptoms or clinical markers are reduced.Alternatively, treatment is “effective” if the progression of a diseaseis reduced or halted. That is, “treatment” includes not just theimprovement of symptoms or markers, but also a cessation or at leastslowing of progress or worsening of symptoms that would be expected inabsence of treatment. Beneficial or desired clinical results include,but are not limited to, alleviation of one or more symptom(s),diminishment of extent of disease, stabilized (i.e., not worsening)state of disease, delay or slowing of disease progression, ameliorationor palliation of the disease state, and remission (whether partial ortotal), whether detectable or undetectable. The term “treatment” of adisease also includes providing relief from the symptoms or side-effectsof the disease (including palliative treatment).

As used herein “preventing” or “prevention” refers to any methodologywhere the disease state does not occur due to the actions of themethodology (such as, for example, administration of a composition orconstruct as described herein). In one aspect, it is understood thatprevention can also mean that the disease is not established to theextent that occurs in untreated controls. Accordingly, prevention of adisease encompasses a reduction in the likelihood that a subject candevelop the disease, relative to an untreated subject (e.g., a subjectwho is not treated with the methods or compositions described herein).

As used herein, the terms “autoimmune condition” and “autoimmunedisease” are used interchangeably and refer to any disease characterizedby abnormal functioning of the immune system and may include, but is notlimited to, achalasia, Addison's disease, adult Still's disease,agammaglobulinemia, alopecia areata, amyloidosis, ankylosingspondylitis, anti-GBM/Anti-TBM nephritis, antiphospholipid syndrome,autoimmune angioedema, autoimmune dysautonomia, autoimmuneencephalomyelitis, autoimmune hepatitis, autoimmune inner ear disease(AIED), autoimmune myocarditis, autoimmune oophoritis, autoimmuneorchitis, autoimmune pancreatitis, autoimmune retinopathy, autoimmuneurticaria, axonal & neuronal neuropathy (AMAN), Baló disease, Behcet'sdisease, benign mucosal pemphigoid, bullous pemphigoid, Castlemandisease, celiac disease, Chagas disease, chronic inflammatorydemyelinating polyneuropathy (CIDP), chronic recurrent multifocalosteomyelitis (CRMO), Churg-Strauss syndrome (CSS), eosinophilicgranulomatosis (EGPA), cicatricial pemphigoid, Cogan's syndrome, coldagglutinin disease, congenital heart block, coxsackie myocarditis, CRESTsyndrome, Crohn's disease, dermatitis herpetiformis, dermatomyositis,Devic's disease (neuromyelitis optica), discoid lupus, Dressler'ssyndrome, endometriosis, eosinophilic esophagitis (EoE), eosinophilicfasciitis, erythema nodosum, essential mixed cryoglobulinemia, Evanssyndrome, fibromyalgia, fibrosing alveolitis, giant cell arteritis(temporal arteritis), giant cell myocarditis, glomerulonephritis,Goodpasture's syndrome, granulomatosis with polyangiitis, Graves'disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, hemolyticanemia, Henoch-Schonlein purpura (HSP), Herpes gestationis or pemphigoidgestationis (PG), hidradenitis suppurativa (HS) (acne inversa),hypogammalglobulinemia, IgA nephropathy, IgG4-related sclerosingdisease, immune thrombocytopenic purpura (ITP), inclusion body myositis(IBM), interstitial cystitis (IC), juvenile arthritis, type 1 diabetes,juvenile myositis (JM), Kawasaki disease, Lambert-Eaton syndrome,leukocytoclastic vasculitis, lichen planus, lichen sclerosus, ligneousconjunctivitis, linear IgA disease (LAD), lupus, lyme disease chronic,Meniere's disease, microscopic polyangiitis (MPA), mixed connectivetissue disease (MCTD), Mooren's ulcer, Mucha-Habermann disease,multifocal motor neuropathy (MMN) or MMNCB, multiple sclerosis,myasthenia gravis, myositis, narcolepsy, neonatal Lupus, neuromyelitisoptica, neutropenia, ocular cicatricial pemphigoid, optic neuritis,palindromic rheumatism (PR), PANDA, paraneoplastic cerebellardegeneration (PCD), paroxysmal nocturnal hemoglobinuria (PNH), ParryRomberg syndrome, pars planitis (peripheral uveitis), Parsonage-Turnersyndrome, pemphigus, peripheral neuropathy, perivenousencephalomyelitis, pernicious anemia (PA), POEMS syndrome, polyarteritisnodosa, polyglandular syndromes type I, II, III, polymyalgia rheumatica,polymyositis, postmyocardial infarction syndrome, postpericardiotomysyndrome, primary biliary cirrhosis, primary sclerosing cholangitis,progesterone dermatitis, psoriasis, psoriatic arthritis, pure red cellaplasia (PRCA), pyoderma gangrenosum, Raynaud's phenomenon, reactivearthritis, reflex sympathetic dystrophy, relapsing polychondritis,restless legs syndrome (RLS), retroperitoneal fibrosis, rheumatic fever,rheumatoid arthritis, sarcoidosis, Schmidt syndrome, scleritis,scleroderma, Sjögren's syndrome, sperm & testicular autoimmunity, stiffperson syndrome (SPS), subacute bacterial endocarditis (SBE), Susac'ssyndrome, sympathetic ophthalmia (SO), takayasu's arteritis, temporalarteritis/Giant cell arteritis, thrombocytopenic purpura (TTP),Tolosa-Hunt syndrome (THS), transverse myelitis, type 1 diabetes,ulcerative colitis (UC), undifferentiated connective tissue disease(UCTD), uveitis, vasculitis, vitiligo, Vogt-Koyanagi-Harada disease. Anautoimmune condition or autoimmune diseases may be caused by, but notlimited to, a natural predisposition, a infection (e.g., bacteria orvirus), drugs, vaccination, environmental triggers (e.g., toxins orchemicals such as dust, silica, oil, benzene, tri- or per-chloroethyleneetc.), stress, cancer, blood or tissue or organ transplantation, orunknown etiology. Autoimmune disorders may result in but not limited tothe destruction of body tissue, abnormal growth of an organ or tissue,changes in organ or tissue function (e.g., changes in blood vessels,connective tissue, function of endocrine glands, joints, muscles, bloodcells, skin, etc.).

As used herein, the term “cancer” refers to a hyperproliferation ofcells that exhibit a loss of normal cellular control that results inunregulated growth, lack of differentiation, local tissue invasion, andmetastasis. The methods and compositions described herein can be usedfor the treatment of solid tumors (e.g., cancer) or non-solid tumors,such as leukemia, blood cell cancers, and the like. Solid tumors can befound in bones, muscles, the brain, or organs, and can be sarcomas orcarcinomas. Where the methods and compositions described herein canovercome barriers of tumor treatment, including, but not limited tobarriers to treatment or inhibition of metastases, it is contemplatedthat aspects of the technology described herein can be used to treat alltypes of solid and non-solid tumor cancers, including cancers not listedin the instant specification. The compositions and methods describedherein, without limitation, include methods of treating cancer, methodsof inhibiting metastases, and methods of inducing an anti-tumor immuneresponse.

As used herein, the terms “subject”, “individual”, “host”, and “patient”are used interchangeably and may refer to any animal, mammal, bird,fish, reptile, and amphibian, for example, human, monkey, dog, cat,horse, pig, cattle, ox, donkey, rabbit, sheep, goat, mouse, rat, guineapig, llama, chicken, goose, duck, turkey, or the like receiving orregistered to receive a therapeutic amount of a composition of thepresent invention for medical care or treatment.

As used herein, the term “injection” refers to any process or methodwhich allows the person skilled in the art to administer any therapeuticto a target site by penetration. Examples of injection are, but notlimited to, subcutaneous, subcuticular, subcapsular, subarachnoid,intradermal, intramuscular, intravenous, intra-arterial,intraventricular, intracapsular, intraorbital, intraocular,intrathoracic, intraperitoneal, intravitreal, retro-orbital, intranasal,intracerebral, intrathymic, intraspinal, intrasternal, intra-articular,intracavernous, intracardiac, intraosseous, intrathecal, transtracheal,epidural, or the like as known in the art. A therapeutic does of thepresent invention may be delivered to a patient by means of controlledrelease, for example but not limited to, implantable pump andimplantable cannulas to provide continuous access to the venous orarterial system.

As used herein, the term “topical application” refers to applying orspreading a composition of the present invention onto surfaces on or inthe body, both internally and/or externally, in a therapeuticallyeffective amount for local and/or systemic treatment. Topicalapplication may be epicutaneuos wherein a composition of the presentinvention may be directly applied onto a localized surface of the skinor mucous membranes. Topical application may include transdermalapplication wherein a composition of the present invention may beabsorbed into the body to obtain systemic delivery and systemicdistribution. For example, a transdermal patch may be applied onto thebody to deliver a therapeutic dose of a composition of the inventionpresented herein. Topical application formulations may include, but arenot limited to, creams, foams, gels, lotions, solutions, ointments,dermal patch, transdermal patches, powder, solid, sponge, tape, vapor,paste, film, liposomes, balm, shampoo, spray, or tincture. A therapeuticdose of a composition of the present invention may be deliveredvaginally (for example a vaginal suppository, vaginal ring, douche,intrauterine device, intravesical infusion, and the like) or urethra.

As used herein, the term “enteral administration” refers to acomposition of the present invention administered via thegastrointestinal tract in a therapeutically effective amount for localor systemic treatment. Enteral administration may include, but is notlimited to, delivery of a composition of the present invention via themouth, sublingual, esophagus, gastric (for example the stomach), smallintestines, large intestines or rectum. Oral delivery of the presentinvention may include, but is not limited to, the use of a capsule,pastille, pill, tablet, solution, gel, suspension, emulsion, syrup,elixir, tincture, mouthwash, lozenges, chewing gum, lollipop,osmotic-controlled release oral delivery system, or the like. Gastricdelivery may involve the use of a tube or nasal passage that leadsdirectly to the stomach, for example, a percutaneous endoscopicgastrostomy tube. Gastric delivery may involve direct injection madethrough the abdominal wall. Rectal delivery may involve, but is notlimited to, the use of a suppository, ointment, enema, murphy drip, orthe like. A therapeutic does of the present invention may be deliveredto a patient by means of controlled release, for example but not limitedto, controlled release drug delivery pellet or pill.

As used herein, the terms “pulmonary system” or “respiratory system” areused interchangeably and refer, but are not limited, to the respiratoryregion, conducting airways, nasal cavity, sinuses, nasopharynx,oropharynx, larynx, trachea, bronchi, bronchioles, respiratorybronchioles, alveolar ducts, alveolar sacs, respiratory epithelium(e.g., alveolar epithelial cells), endothelial cells, or the like.

As used herein, the terms “pulmonary delivery” and “pulmonaryadministration” are used interchangeably and refer to delivering acomposition of the present invention to the respiratory system throughthe respiratory route, including but not limited to, intranasaladministration, oral administration, and oral inhalative administration(e.g., intratracheal instillation and intratracheal inhalation) of atherapeutically effective amount for local or systemic treatment.Pulmonary delivery of a therapeutically effective amount of acomposition of the present invention may be achieved by dispersion, forexample by using a syringe. Pulmonary delivery of a composition of thepresent invention may be achieved by aerosol administration, whereinaerosol administration may deposit a therapeutically effective amount ofthe present invention by gravitational sedimentation, inertialimpaction, or diffusion.

Pulmonary delivery of a therapeutically effective amount of acomposition of the present invention may be deposited on any mucus layerof the respiratory system, for example, but not limited to, the mucuslayer which coats the walls of conducting airways, the smaller airway,and/or alveolar space.

As used herein, an “appropriate control” refers to an untreated,otherwise identical cell or population (e.g., a subject who was notadministered the composition described herein, or was administered byonly a subset of agents provided herein, as compared to a non-controlcell).

As used herein, a “reference level” can refer to one or more parametersor markers as measured for a normal, otherwise unaffected cellpopulation or tissue (e.g., a biological sample obtained from a healthysubject, or a biological sample obtained from the subject at a priortime point, or a biological sample that has not yet been contacted witha pathogen as described herein). For measuring or monitoring therapeuticefficacy, a level determined prior to treatment or earlier in treatmentcan also provide a reference level for a given parameter or value.

As used herein, the term “modulates” refers to an effect includingincreasing or decreasing a given parameter as those terms are definedherein.

The terms “increased,” “increase,” “increases,” or “enhance” or“activate” are all used herein to generally mean an increase of aproperty, level, or other parameter by a statistically significantamount; for the avoidance of any doubt, the terms “increased”,“increase” or “enhance” or “activate” means an increase of at least 10%as compared to a reference level, for example an increase of at leastabout 20%, or at least about 30%, or at least about 40%, or at leastabout 50%, or at least about 60%, or at least about 70%, or at leastabout 80%, or at least about 90% or up to and including a 100% increaseor any increase between 10-100% as compared to a reference level, or atleast about a 2-fold, or at least about a 3-fold, or at least about a4-fold, or at least about a 5-fold or at least about a 10-fold increase,at least about a 20-fold increase, at least about a 50-fold increase, atleast about a 100-fold increase, at least about a 1000-fold increase ormore as compared to a reference level. For example, increasing activitycan refer to activating a receptor or a signaling pathway (e.g.,antibody production or inflammation).

The terms “decrease”, “reduced”, “reduction”, or “inhibit” are all usedherein to mean a decrease or lessening of a property, level, or otherparameter by a statistically significant amount. In some embodiments ofany of the aspects, “reduce,” “reduction” or “decrease” or “inhibit”typically means a decrease by at least 10% as compared to a referencelevel (e.g., the absence of a given treatment) and can include, forexample, a decrease by at least about 10%, at least about 20%, at leastabout 25%, at least about 30%, at least about 35%, at least about 40%,at least about 45%, at least about 50%, at least about 55%, at leastabout 60%, at least about 65%, at least about 70%, at least about 75%,at least about 80%, at least about 85%, at least about 90%, at leastabout 95%, at least about 98%, at least about 99%, or more. As usedherein, “reduction” or “inhibition” does not encompass a completeinhibition or reduction as compared to a reference level. “Completeinhibition” is a 100% inhibition as compared to a reference level. Adecrease can be preferably down to a level accepted as within the rangeof normal for an individual without a given disorder.

As used herein the term “comprising” or “comprises” is used in referenceto compositions, methods, and respective component(s) thereof, that areessential to the method or composition, yet open to the inclusion ofunspecified elements, whether essential or not.

As used herein the term “consisting essentially of” refers to thoseelements required for a given embodiment. The term permits the presenceof elements that do not materially affect the basic and novel orfunctional characteristic(s) of that embodiment.

The term “consisting of” refers to compositions, methods, and respectivecomponents thereof as described herein, which are exclusive of anyelement not recited in that description of the embodiment.

As used in this specification and the appended claims, the singularforms “a,” “an,” and “the” include plural references unless the contextclearly dictates otherwise. Thus for example, references to “the method”includes one or more methods, and/or steps of the type described hereinand/or which will become apparent to those persons skilled in the artupon reading this disclosure and so forth. Similarly, the word “or” isintended to include “and” unless the context clearly indicatesotherwise. Although methods and materials similar or equivalent to thosedescribed herein can be used in the practice or testing of thisdisclosure, suitable methods and materials are described below.

The abbreviation, “e.g.” is derived from the Latin exempli gratia, andis used herein to indicate a non-limiting example. Thus, theabbreviation “e.g.” is synonymous with the term “for example.”

The abbreviation, “etc.” is derived from the Latin et cetera, and isused herein to indicate a non-limiting list. Thus, the abbreviation“etc.” is synonymous with the term “and other similar things”, or “andso forth”.

Other than in the operating examples, or where otherwise indicated, allnumbers expressing quantities of ingredients or reaction conditions usedherein should be understood as modified in all instances by the term“about.” The term “about” when used in connection with percentages canmean±1%.

The term “statistically significant” or “significantly” refers tostatistical significance and generally means a two-standard deviation(2SD) difference, above or below a reference value. Additionaldefinitions are provided in the text of individual sections below.

It should be understood that this invention is not limited to theparticular methodology, protocols, and reagents, etc., described hereinand as such may vary. The terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to limit thescope of the present invention, which is defined solely by the claims.

As used herein and in the claims, the singular forms include the pluralreference and vice versa unless the context clearly indicates otherwise.The term “or” is inclusive unless modified, for example, by “either.”Other than in the operating examples, or where otherwise indicated, allnumbers expressing quantities of ingredients or reaction conditions usedherein should be understood as modified in all instances by the term“about.”

Unless otherwise explained, all technical and scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which this disclosure belongs.

It is to be understood that the foregoing description and the followingexamples are illustrative only and are not to be taken as limitationsupon the scope of the invention. Various changes and modifications tothe disclosed embodiments, which will be apparent to those of skill inthe art, may be made without departing from the spirit and scope of thepresent invention. Further, all patents, patent applications, andpublications identified are expressly incorporated herein by referencefor the purpose of describing and disclosing, for example, themethodologies described in such publications that might be used inconnection with the present invention. These publications are providedsolely for their disclosure prior to the filing date of the presentapplication. Nothing in this regard should be construed as an admissionthat the inventors are not entitled to antedate such disclosure byvirtue of prior invention or for any other reason. All statements as tothe date or representation as to the contents of these documents arebased on the information available to the applicants and do notconstitute any admission as to the correctness of the dates or contentsof these documents.

All patents and other publications identified are expressly incorporatedherein by reference for the purpose of describing and disclosing, forexample, the methodologies described in such publications that could beused in connection with the present invention. These publications areprovided solely for their disclosure prior to the filing date of thepresent application. Nothing in this regard should be construed as anadmission that the inventors are not entitled to antedate suchdisclosure by virtue of prior invention or for any other reason. Allstatements as to the date or representation as to the contents of thesedocuments is based on the information available to the applicants anddoes not constitute any admission as to the correctness of the dates orcontents of these documents.

Some embodiments of the technology described herein can be definedaccording to any of the following numbered paragraphs:

-   -   1. An engineered extracellular vesicle comprising:        -   at least one fusion polypeptide comprising:            -   (i) at least one protein of interest (POI) domain or a                fragment thereof; and            -   (ii) at least one vesicle targeting domain,        -   wherein the POI domain is in an extracellular position            relative to a lipid membrane of the extracellular vesicle.    -   2. The engineered extracellular vesicle of paragraph 1, wherein        the extracellular vesicle is an exosome.    -   3. The engineered extracellular vesicle of paragraph 1 or        paragraph 2, wherein the protein of interest (POI) domain or a        fragment thereof is a N-terminal domain of the fusion        polypeptide.    -   4. The engineered extracellular vesicle of any one of paragraphs        1-3, wherein the vesicle targeting domain is a C-terminal domain        of the fusion polypeptide.    -   5. The engineered extracellular vesicle of any one of paragraphs        1-4, wherein the fusion polypeptide comprises at least two POI        domains and/or at least two exosome targeting domains.    -   6. The engineered extracellular vesicle of any one of paragraphs        1-5, wherein the fusion polypeptide further comprises a peptide        linker.    -   7. The engineered extracellular vesicle of any one of paragraphs        1-6, wherein the fusion polypeptide further comprises a fragment        crystallizable region (Fc) domain.    -   8. The engineered extracellular vesicle of any one of paragraphs        1-7, wherein the vesicle targeting domain is in a luminal        position relative to the lipid membrane of the extracellular        vesicle.    -   9. The engineered extracellular vesicle of any one of paragraphs        1-7, wherein the vesicle targeting domain in an exterior        position relative to the lipid membrane of the extracellular        vesicle.    -   10. The engineered extracellular vesicle of any one of        paragraphs 1-9, wherein the POI domain is selected from the        group consisting of: Table 1.    -   11. The engineered extracellular vesicle of any one of        paragraphs 1-10, wherein the POI domain is PD-L1 or a fragment        thereof.    -   12. The engineered extracellular vesicle of any one of        paragraphs 1-11, wherein the POI domain is PD-L2 or a fragment        thereof.    -   13. The engineered extracellular vesicle of any one of        paragraphs 1-12, wherein the POI domain is FGL1 or a fragment        thereof.    -   14. The engineered extracellular vesicle of any one of        paragraphs 1-13, wherein the POI domain is 4-1BBL or a fragment        thereof.    -   15. The engineered extracellular vesicle of any one of        paragraphs 1-14, wherein the POI domain is CTLA-4 or a fragment        thereof.    -   16. The engineered extracellular vesicle of any one of        paragraphs 1-15, wherein the POI domain substantially binds to        one or more of a target polypeptide.    -   17. The engineered extracellular vesicle of paragraph 16,        wherein the target polypeptide is selected from the group        consisting of: Table 2.    -   18. The engineered extracellular vesicle of any one of        paragraphs 1-17, wherein the vesicle targeting domain is        selected from the group consisting of: Table 3.    -   19. The engineered extracellular vesicle of any one of        paragraphs 1-18, wherein the linker is in an exterior position        relative to the lipid membrane of the extracellular vesicle.    -   20. The engineered extracellular vesicle of any one of        paragraphs 1-18, wherein the linker is a transmembrane linker.    -   21. The engineered extracellular vesicle of any one of        paragraphs 1-18, wherein the linker is in a luminal position        relative to the lipid membrane of the extracellular vesicle.    -   22. The engineered extracellular vesicle of any one of        paragraphs 1-21, wherein the extracellular vesicle does not        comprise an endogenous POI polypeptide.    -   23. A composition comprising a plurality of the engineered        extracellular vesicles of any one of paragraphs 1-22.    -   24. The composition of paragraph 23, further comprising a        pharmaceutically acceptable carrier.    -   25. An engineered extracellular vesicle comprising:        -   (a) a first fusion polypeptide comprising:            -   (i) at least one protein of interest (POI) domain or a                fragment thereof; and            -   (ii) at least one vesicle targeting domain,        -   wherein the at least one POI domain is in an extracellular            position relative to a lipid membrane of the extracellular            vesicle,        -   (b) a second fusion polypeptide comprising:            -   (i) at least one protein of interest (POI) domain or a                fragment thereof; and            -   (ii) at least one vesicle targeting domain,        -   wherein the POI domain is in an extracellular position            relative to a lipid membrane of the extracellular vesicle,        -   and wherein the at least one vesicle targeting domain is            within a lipid membrane of the extracellular vesicle.    -   26. A composition comprising two or more of the engineered        extracellular vesicles selected from any one of paragraphs 1-25.    -   27. An extracellular vesicle composition comprising:        -   a plurality of artificial synapses,        -   wherein each artificial synapse comprises (i) an            extracellular vesicle; (ii) one or more sticky binders;            and (iii) one or more signaling domains.    -    The composition of paragraph 27, wherein the extracellular        vesicle comprises an exosome.    -   28. The composition of paragraph 27, wherein the one or more        sticky binders is selected from the group consisting of: a GPI        anchor, a fatty acetylation site, and a prenylation site.    -   30. The composition of paragraph 27, wherein the signaling        domain comprises one or more of: PD-L1, PD-L2, CTLA-4 (CD152),        4-1BBL (CD137L), HVEM (CD270), FGL1, OX-2 (CD200), Galectin-9,        PVR (CD155), Nectin-2 (CD112) isoform alpha, Nectin-2 (CD112)        isoform beta, Nectin-2 (CD112) isoform delta, IL-10, TSG-6,        B7-H3 (CD276), B7-H4 (VTCN1), B7-H5 (VISTA), B7-H7 (HHLA2),        BTNL1, VSIG8, VSIG3 (IGSF11), VSIG4, TIM-3 (HAVCR2), TIM-4        (TIMD4), CEACAM1, BTN3A1, BTN3A2, BTN2A1, BTNL8, BTN2A2, BTN1A1,        TIGIT, CD27L (CD70), CD30L (CD153), GITRL, CD40L (CD154), LIGHT        (CD258), TL1, CD80, CD86, LFA-3 (CD58), SLAM (CD150), CD40,        CD28, CD28H, CD2, LFA-3 (CD58), CD48, CD226, DR3, DcR3, FasL,        TIM-1 (CD365), PD-1, or active fragment thereof.    -   29. A method of producing the engineered extracellular vesicle        or the composition of any one of paragraphs 1-30, comprising:        -   (a) providing a population of cells expressing a vector            construct encoding one or more sticky binder and one or more            signaling domains; and        -   (b) isolating a plurality of artificial synapses from the            population of cells.    -   30. A method of producing the engineered extracellular vesicle        or the composition of any one of paragraphs 1-30, comprising:        -   (a) providing a population of cells expressing a vector            construct encoding one or more sticky binder and one or more            signaling domains; and        -   (b) isolating a plurality of artificial synapses from the            population of cells; and        -   (c) purifying the plurality of artificial synapses from the            population of cells.    -   33. The method of paragraph 31 or paragraph 32, the isolating is        via size exclusion chromatography.    -   34. The method of paragraph 32, wherein the purifying is via        multimodal chromatography.    -   35. The method of any of paragraphs 31-34, further comprising        performing an assay for POI binding to a target polypeptide.    -   36. The method of paragraph 35, wherein the vector construct        further encodes a promoter.    -   37. The method of paragraph 36, wherein the promoter is a        tissue-specific promoter or an inducible promotor.    -   38. A method of modulating inflammation in a subject, the method        comprising:        -   administering a composition comprising a plurality of            engineered extracellular vesicles to a subject in need            thereof,        -   wherein the engineered extracellular vesicles comprise at            least one fusion polypeptide comprising:            -   (i) at least one protein of interest (POI) domain or a                fragment thereof; and            -   (ii) at least one vesicle targeting domain.    -   39. The method of paragraph 38, wherein the extracellular        vesicle comprises an exosome.    -   40. The method of any one of paragraphs 38-39, further        comprising selecting a subject that has or is suspected of        having an autoimmune disease or an inflammatory disease or        condition.    -   41. The method of any one of paragraphs 38-40, wherein the        vesicle targeting domain is selected from the group consisting        of: a Glycosylphosphatidylinositol (GPI) anchor, a fatty        acetylation site, and a prenylation site.    -   42. The method of any one of paragraphs 38-41, wherein the        vesicle targeting domain is a GPI anchor.    -   43. The method of any one of paragraphs 38-41, wherein the        vesicle targeting domain is C1C2.    -   44. The method of any one of paragraphs 38-43, wherein the        protein of interest (POI) domain comprises one or more of:        PD-L1, PD-L2, CTLA-4 (CD152), 4-1BBL (CD137L), HVEM (CD270),        FGL1, OX-2 (CD200), Galectin-9, PVR (CD155), Nectin-2 (CD112)        isoform alpha, Nectin-2 (CD112) isoform beta, Nectin-2 (CD112)        isoform delta, IL-10, TSG-6, B7-H3 (CD276), B7-H4 (VTCN1), B7-H5        (VISTA), B7-H7 (HHLA2), BTNL1, VSIG8, VSIG3 (IGSF11), VSIG4,        TIM-3 (HAVCR2), TIM-4 (TIMD4), CEACAM1, BTN3A1, BTN3A2, BTN2A1,        BTNL8, BTN2A2, BTN1A1, TIGIT, CD27L (CD70), CD30L (CD153),        GITRL, CD40L (CD154), LIGHT (CD258), TL1, CD80, CD86, LFA-3        (CD58), SLAM (CD150), CD40, CD28, CD28H, CD2, LFA-3 (CD58),        CD48, CD226, DR3, DcR3, FasL, TIM-1 (CD365), PD-1, or active        fragment thereof.    -   45. The method of any one of paragraphs 38-44, wherein the        protein of interest (POI) domain is PD-L1 or a fragment thereof.    -   46. The method of any one of paragraphs 38-44, wherein the        protein of interest (POI) domain is PD-L2 or a fragment thereof.    -   47. The method of any one of paragraphs 38-44, wherein the        protein of interest (POI) domain is CTLA-4 or a fragment        thereof.    -   48. The method of any one of paragraphs 38-44, wherein the        protein of interest (POI) domain is HVEM or a fragment thereof.    -   49. The method of paragraph 40, wherein the inflammatory disease        and/or condition is acute.    -   50. The method of paragraph 40, wherein the inflammatory related        disease and/or condition is chronic.    -   51. The method of paragraph 38, wherein administering the        composition comprises injection, topical administration, or        inhalation.    -   52. Use of a composition comprising a plurality of engineered        extracellular vesicles, the engineered extracellular vesicles        each comprising:        -   at least one fusion polypeptide comprising:            -   (i) at least one protein of interest (POI) domain or a                fragment thereof; and            -   (ii) at least one vesicle targeting domain        -   for the treatment of an inflammatory disease or condition.    -   53. Use of a composition comprising a plurality of engineered        extracellular vesicles, the engineered extracellular vesicles        each comprising:        -   at least one fusion polypeptide comprising:            -   (i) at least one protein of interest (POI) domain or a                fragment thereof; and            -   (ii) at least one vesicle targeting domain        -   for the treatment of an autoimmune disease or condition.    -   54. Use of a composition comprising a plurality of engineered        extracellular vesicles, the engineered extracellular vesicles        each comprising:        -   at least one fusion polypeptide comprising:            -   (i) at least one protein of interest (POI) domain or a                fragment thereof; and            -   (ii) at least one vesicle targeting domain        -   for the treatment of cancer.

EXAMPLES

The following examples are provided by way of illustration, notlimitation.

Example 1 Design of Artificial Synapse

As described, artificial synapses are engineered to induce and propagatebiological signaling, including for example, antagonist and agonistsignaling. Artificial synapses are designed to include hallmarkbiophysical and biochemical features of extracellular vesicles, furtherincluding vesicle targeting domains and signaling domains. Vesicletargeting domains capable of attaching to extracellular vesicles such asexosomes, signaling domains, optionally including a linker (e.g., Fclinker), can be organized in genetic vector constructs. Designs areshown in FIG. 1.

Sticky binders are extracellular vesicle targeting sequences.Preliminary extracellular vesicle targeting sequences of interest arefrom, but not limited to, 4F2 (CD98), ADAM 10, CD298, TFR2,transmembrane domains of CD9, MARCKS, KRAS, etc. or the like asappreciate by one of ordinary skill in the art. The Inventors discoveredhigh efficiency when proteins are engineered with a GPI domain.Optionally, linker regions such as an Fc linker between the vesicletargeting domains and signaling domains can be added.

A variety of signaling domains are of interest with proof-of-conceptexamples including PD-L1, PD-L2 and CTLA-4 (CD152). Artificial synapsesincluding these three signaling domains are shown in FIGS. 2-5.

Each of these elements are described in the following non-limitingexamples.

Example 2 Genetic Constructs

Examples of constructs including these variable elements (e.g., stickybinders GPI or C1C2, or signaling domains including PD-L1, PD-L2 andCTLA-4 (CD152) were engineered into vectors shown in FIGS. 2-5.

Example 3 Purification of hPD-L1 Tagged Artificial Synapses by aMultimodal Resin Marketed for Exosome Purification

Upon expression of hPD-L1-Fc-GPI in mammalian cells, artificial synapseswere further purified using a size exclusion resin marketed for exosomepurification. Large MW artificial synapses elute in the first fractionas shown by the high hPD-L1 concentration and exosome quantity (2.26E9artificial synapses/ml) in elution 1. Clean in place (CIP) fractionsshow bound and eliminated proteins from the Inventors' exosome elution.Results are shown in FIG. 6.

Example 4 hPDL1-Fc-GPI Exosome Purification—Size ExclusionChromatography Column

Artificial synapses engineered from exosomes such as hPDL1-Fc-GPI afterelution from size exclusion resin marketed for exosome purification canbe further purified via a size exclusion column as shown here. Using asize exclusion chromatography (SEC), artificial synapses elute infractions 7-9. Total protein (determined by qBit) and hPD-L1 ng/ml(determined by ELISA) of each fraction is shown in the graph. Bars showexosome number per ml (i.e. 1E10 artificial synapses/ml etc.). Fractions7-9 contain >99% purified artificial synapses. Fractions 7-9 are pooledand may be concentrated using a filtration device, for example a 10KMWCO Amicon Centrifugal Filter. Final purified product is filteredthrough a low protein binding 0.2 μM or 0.45 μm filter, for example aPES filter. Results are shown in FIG. 7.

Example 5 hPD-L1 Expression on Artificial Synapses

Exosome quantity and hPD-L1 concentration was determined in SECfractions 7-9. Knowing the molecular weight of engineered hPD-L1, theInventors can determine the number of hPD-L1 molecules per exosome to beapproximately between 12 to 40 PD-L1/exosome. This value is consistentbetween different purification runs and constructs. Results are shown inFIG. 8.

Example 6 Purification of hPD-L2-Fc-GPI Artificial Synapses ViaMultimodal Resin Chromatography Marketed for Exosome Purification

This graph shows Abs 280 of multimodal resin chromatography fractionsand quantity of hPDL2 in indicated fractions. Artificial synapses elutedin Elution 1.

Clean in place (CIP) fractions show bound and eliminated proteins fromthe Inventors' exosome elution. Results are shown in FIG. 9.

Example 7 PD-L2 Purification Via Size Exclusion Chromatography

Artificial synapses engineered from artificial synapses such ashPDL2-GPI after elution from size exclusion resin size exclusion resinmarketed for exosome purification are further purified via sizeexclusion chromatography as shown. Results are shown in FIG. 10.

Example 8 hCTLA4-Fc-GPI Exosome Purification Via Size ExclusionChromatography

Using size exclusion chromatography marketed for exosome purification,artificial synapses elute in fractions 7-9. Total protein (determined byqBit) and hPD-L1 ng/ml (determined by ELISA) of each fraction is shownin the graph. Fractions 7-9 are pooled and contain >99% purifiedartificial synapses. Pooled artificial synapses engineered fromartificial synapses fractions may then be concentrated using afiltration device, for example al OK MWCO Amicon. Final purified productis filtered through a low protein binding filter, for example a 0.2 μmor 0.45 um PES filter. Results are shown in FIG. 11.

Example 9 PD-L1 and PD-L2 In Vitro Assay from DiscoverX

To perform this validation method, the Inventors modified the PathHunterPD-1 Signaling Bioassay from DiscoverX Briefly, the PathHunter PD-1Signaling Bioassay relies on the well-established PathHunter EnzymeFragment Complementation (EFC) technology to interrogate receptoractivity. EFC consists of a split β-galactosidase (β-gal) enzyme: theEnzyme Donor (ED) and Enzyme Acceptor (EA) fragments which independentlyhave no β-gal activity. However, when forced to complement they form anactive β-gal enzyme that will hydrolyze substrate to produce achemiluminescent signal. The PathHunter PD-1 Signaling Bioassay consistsof human cells engineered to stably express an ED-tagged PD-1 receptor,while EA is fused to the phosphotyrosine-binding SH2 domain of theintracellular signaling protein, SHP1. Ligand or antibody-inducedactivation of the receptor results in phosphorylation of the receptor'scytosolic tail. The SH2-domain fused to EA binds the phosphorylatedreceptor, forcing complementation of ED and EA, resulting in formationof an active β-gal enzyme, which hydrolyzes the substrate to produce achemiluminescent signal. Full-length PD-1 receptor was engineered with asmall β-gal fragment (ED in red) fused to its C-terminus, and theSH2-domain of SHP1 was engineered with the complementing β-gal fragment(EA). These constructs were stably expressed in Jurkat cells (producedby DiscoverX), while PD-L1 and PD-L2 was stably expressed on artificialsynapses produced by Diadem Biotherapeutics. Artificial synapses wereengineered to have surface expressed human PD-L1 or PD-L2. Briefly, thegene sequence coding for the extracellular domain of human PD-L1 orPD-L2 was linked to the exosome via a glycosylphosphatidylinositol (GPI)linker with an Fc domain between the linker and PD-L1 or PD-L2(PD-L1-Fc-GPI and PD-L2-Fc-GPI). Additional variations of the Inventors'PD-L1 and PD-L2 artificial synapses include cloning a C1C2 linker (fromMFGE8) in place of the GPI linker, and with or without the Fc domain.The Inventors also cloned murine versions of PD-L1 and PD-L2extracellular domains in place of the human PD-L1 and PD-L2 allvariations. Ligand engagement, through addition of ligand-presentingartificial synapses, results in phosphorylation of PD-1, leading to therecruitment of SHP1-EA

The Inventors obtained approximately 1000× higher increase in RelativeLight Units (RLU) in Jurkat signaling cells treated with PD-L1 or PD-L2labeled artificial synapses when compared to soluble PD-L1-Fc orPD-L2-Fc ligand, respectively. Meaning, it took 1000× less ug/ml ofPD-L1 or PD-L2 on artificial synapses than solubilized PD-L1-Fc or PD-L2ligand to achieve the same RLU signaling. Results are shown in FIG. 12.

Example 10 PD-L1 In Vivo Assay—Experimental Autoimmune Uveoretinitis(EAU) in Lewis Rats Bioassay

Experimental autoimmune uveoretinitis (EAU) is an organ-specific, Tlymphocyte-mediated autoimmune disease, which serves as a model forseveral human ocular inflammations of an apparently autoimmune nature.There is a statistically significant initial reduction in EAU in mPDL1artificial synapse treated rats via either the intravitreal andintravenous delivery modes. 2nd intravitreal and 3rd intravenousinjections are performed on Day 12. There appears to be a more rapidrate of resolution in the IX intravitreal and intravenous groups. (C)Simplified view of aforementioned results. (D) Weight of rats wasmonitored throughout the study. 3rd intravitreal and 4th intravenousinjections are performed on Day 16. There does not appear to be anysignificant change in EAU in any of the test groups. The aforementionedresults provide proof of principle of successfully immunizing the ratswith human cell derived artificial synapses with mouse PDL1 injectedinto rats. Results are shown in FIG. 13.

Example 11 Engineered Exosome Multivalent Display

The inventors have developed the following 3 types of protein display onor within exosomes:

-   -   Type I membrane proteins wherein the N-Terminus is on the        luminal (interior) side of the exosome membrane and the        C-Terminus is on the exterior of the exosome.    -   Type II membrane proteins wherein the N-Terminus is on the        exterior while the C-Terminus is on the interior.    -   Luminal internally loaded proteins which are linked to the        exosome by a Myristoylation/Palmitoylation site which attaches        proteins to the interior of the exosome membrane.

FIGS. 14-21 demonstrate the various embodiments of the engineeredextracellular vesicles.

Additional embodiments or ligands displayed on the exosome surface (TypeI and Type II membrane proteins) and internal luminal display caninclude the following:

-   -   Type I: PD-L1, PD-L2, FGL1, OX40L    -   Type II: 4-1BBL, GITRL, CD27L, CD30L    -   Luminal: NanoLuc® luciferase; Green fluorescent protein (GFP)        (e.g., eGFP, etc.); Red fluorescent protein (RFP) (e.g.,        mScarlet, mCherry, mRuby, tdTomato, etc.); Cyan fluorescent        protein (CFP); Yellow fluorescent protein (YFP); A therapeutic        protein; and CRISPR/CAS-9

FIG. 20 shows an exemplary multiple protein display construct. Sequencessuch as P2A, E2A, F2A, and T2A induce ribosomal slippage which preventpeptide bond formation, meaning that a single mRNA transcript with a 2Asequence will result in two separate peptides after translation. Thisallows the expression of two separate proteins from one promoter regionand thus loading of two proteins on an exosome. Any combination of theproteins of interest domains provided herein can be engineered.Furthermore, a cell line with multiple transgene inserts under separatepromoter control. Either method can be used to label Type I, Type II,and luminal display proteins.

Example 12a Designed and Engineered Human Fusion Polypeptide Constructs

The inventors have designed, engineered, and purified the followinghuman fusion polypeptide constructs for therapeutic use (FIG. 5A-FIG.5WW):

-   -   pEF5-FRT-hPDL1-C1C2 (FIG. 5I)    -   pEF5-FRT-hPDL2-C1C2 (FIG. 5J)    -   pEF5-FRT-hPDL1-GPI-P2A-hFGL1-GPI (FIG. 5E)    -   pEF5-FRT-hCTLA4-Fc-GPI (FIG. 5C)    -   pEF5-FRT-hPDL2-Fc-GPI (FIG. 5H)    -   pEF5-FRT-hPD-L1-GPI-P2A-hHVEM-GPI (FIG. 5D)    -   pEF5-FRT-hPDL1-GPI (FIG. 5F)    -   pcDNA5-FRT-hSecPDL1-GPI (FIG. 5O)    -   pcDNA5-FRT-hPDL1-GPI (FIG. 5F)    -   pcDNA5-FRT-hPDL1-Link-GPI (FIG. 5T)    -   pcDNA5-FRT-4F2-h41BBL (FIG. 5K)    -   pcDNA5-FRT-Tfr2-h41BBL (FIG. 5P)    -   pEF5-FRT-hPDL1-Fc-GPI (FIG. 5G)    -   pcDNA5-FRT-CD9tm3-h41BBL (FIG. 5Q)    -   pcDNA5-FRT-hPDL1-Fc-GPI (FIG. 5G)    -   pcDNA5-FRT-hPDL1-4Fc-CD9tm2 (FIG. 5RR)    -   pcDNA5-FRT-hPDL1-Fc-CD9tm2KRAS (FIG. 5UU)    -   pcDNA5-FRT-hPDL1-4Fc-CD9tm2KRAS (FIG. 5SS)    -   pcDNA5-FRT-hPDL1-4Fc-GPI (FIG. 5L)    -   pcDNA5-FRT-hPDL1-ADAM10 (FIG. 5QQ)    -   pcDNA5-FRT-MyrPalm-4F2-h41BBL (FIG. 5R)    -   pcDNA5-FRT-MyrPalm-h41BBL (FIG. 5S)    -   pcDNA5-FRT-hPDL1-Fc-CD9tm2 (FIG. 5TT)    -   pcDNA5-FRT-hSecPDL1-CD9tm4 (FIG. 5W)    -   pcDNA5-FRT-hSecPDL1-CD9tm2KRas (FIG. 5V)    -   pcDNA5-FRT-hSecPDL1-CD9tm2 (FIG. 5U)    -   pcDNA5-FRT-hSecPDL1-CD81 (FIG. 5X)    -   pEF5-FRT-hCD200-Fc-GPI (FIG. 5Y)    -   pEF5-FRT-hCD200-GPI (FIG. 5BB)    -   pEF5-FRT-hTSG6-GPI (FIG. 5FF)    -   pEF5-FRT-hPDL2-GPI (FIG. 5EE)    -   pEF5-FRT-hFGL-1-GPI (FIG. 5Z)    -   pEF5-FRT-hHVEM-GPI (FIG. 5DD)    -   pEF5-FRT-hGal9-GPI (FIG. 5CC)    -   pEF5-FRT-hHVEM-Fc-GPI (FIG. 5GG); and    -   pEF5-FRT-hGal9-Fc-GPI (FIG. 5AA)

Example 12b Designed and Engineered Fusion Polypeptide Constructs

The inventors have designed, engineered, and purified the followingmouse fusion polypeptide constructs for therapeutic use (FIG. 5A-FIG.5WW):

-   -   pcDNA5-FRT-mPDL1-mFc-CD9tm2KRAS (FIG. 5WW)    -   pcDNA5-FRT-mPDL1-mFc-CD9tm2 (FIG. 5VV)    -   pcDNA5-FRT-mPDL1-mFc-GPI (FIG. 5NN)    -   pcDNA5-FRT-mPDL1-GPI (FIG. 5KK)    -   pEF5-FRT-mPDL2-GPI (FIG. 5.OO)    -   pEF5-FRT-mPDL1-GPI-P2A-mHVEM-GPI (FIG. 5PP)    -   pEF5-FRT-mPDL1-GPI (FIG. 5KK)    -   pEF5-FRT-mPDL2-Fc-GPI (FIG. 5MM)    -   pEF5-FRT-mPDL1-Fc-GPI (FIG. 5JJ)    -   pEF5-FRT-mCTLA4-Fc-GPI (FIG. 5HH)    -   pEF5-FRT-mPDL1-C1C2 (FIG. 5II); and    -   pEF5-FRT-mPDL2-C1C2 (FIG. 5LL).

Example 12c Designed and Engineered Luminal Loaded Fusion PolypeptideConstructs

The inventors have designed, engineered, and purified the followingfusion polypeptide constructs for internal luminal loading of the fusionpolypeptide:

-   -   pcDNA5-FRT-Myr-NanoLuc (FIG. 5M)    -   pcDNA5-FRT-Myr-mScarlet (FIG. 5N)

Example 13 Purification of Exosomes Labeled with Type I Membrane FusionPolypeptides

The inventors have purified engineered EVs, including hPD-L1-GPI;hPDLI-Fc-GPI; hPDL2-Fc-GPI; hCTLA4-Fc-GPI; mPDL1-GPI; and mPD-L1-Fc-GPI.The process for purification and analytical processing of the engineeredEVs are shown in the flow chart provided in FIG. 2L

Size exclusion chromatography was performed to purify hPD-L1-GPI (no Fc)exosomes (FIG. 24). Protein, RNA and DNA measurements in SEC fractions.Invitrogen Qubit fluorometric assays were used to measure biomoleculesfrom unmodified concentrated cell media SEC fractions or hPD-L1-Exo-Tagconcentrated cell media SEC fractions. PD-L1 was measured using an R&Dsystems PD-L1 ELISA kit. Dot-blot immunoblot analysis of SEC fractions.A 96-well dot blot apparatus was used to immobilize 50 ul of each SECfraction onto PVDF. Exosome size and concentration was measured infraction 7 by tunable resistive pulse sensing (TRPS). It was confirmedthat GPI anchors the hPD-L1 fusion protein onto the exosomes (FIG. 25).

Furthermore, a commercially available multimodal exosome purificationresin was also used to purify and isolate PD-L1-GPI exosomes andPD-L1-Fc-GPI exosomes. Fraction 7 was further analyzed by dot blots(FIG. 28A-28B). In particular, FIG. 28B shows SEC purification resultsof various embodiments of human PD-L1 displayed on the surface ofextracellular vesicles. One embodiment is the hPD-L1-4Fc-GPI (CMV)construct as seen in the top dot blot (stained with rabbit monoclonalanti-PD-L1 antibody). Another embodiment is the hPD-L1-4Fc-GPI (EF1a) asseen in the top dot blot (stained with rabbit monoclonal anti-PD-L1antibody).

Large MW exosomes elute in the first fraction as shown by the highhPD-L1 concentration and exosome quantity (2.26E9 exosomes/ml) inelution 1. Clean in place (CIP) fractions show bound and eliminatedproteins from our exosome elution. Exosome quantity and hPD-L1concentration was determined in SEC fractions 7-9. Knowing the molecularweight of engineered hPD-L1, we can determine the number of hPD-L1molecules per exosome to be approximately 12 PD-L1/exosome. This valueis consistent between different purification runs and constructs (FIG.8).

Human hPD-L2 and hCTLA-4-Fc-GPI SEC fractions were purified. Inaddition, purification of the mouse PD-L1-FcGPI exosomes was performed(FIG. 29). The mouse Fc-PD-L1 expressing exosomes have a higher valencythan those that do not comprise the Fc linker.

Example 14 Comparative Proteomics Analysis of the Engineered EVs

Fc-GPI enables high density display and has a higher abundance thanendogenous PTGFRN or CD81. Therefore, comparison proteomics oftransprotein expression and surface labeling on the engineered exosomes,hPD-L1-Fc-GPI; hPD-L2-Fc-GPI; and hCTLA-Fc-GPI, was performed todetermine the effects on endogenous protein expression in engineeredexosomes. It was confirmed that the fusion polypeptide expression doesnot affect the relative expression of native and associated exosomeproteins. However, the trans protein may crowd out abundant proteinslike CD81 (data not shown).

Example 15 Scale-Up Production and Purification of mPD-L1-Fc-GPIExosomes Using Microcarriers in a Stirred Tank Single-Use Bioreactor(STR)

1E7 HEK 293 cells were utilized for the production of mPDL1-Fc-GPIexosomes. Cells were passaged on SoloHill® Microcarriers up to Passage4, at which point cells were expanded in a 2.5 L Stirred Tank Single-UseBioreactor. Passage 4 cells were cultured for an additional 5 days andmedia was harvested on Day 5 and used for exosome purification. Thegeneral aim and process is provided below

AIM: Utilize SoloHill's Xeno-free microcarrier technology to scale upcells for engineering EVs and evaluate Microcarrier-stir tank bioreactortechnology for production of therapeutic exosomes in the Xeno-freemedium conditions.

Passage 1:

Thaw vial (1.00E+07) of cells and seed Corning T-150 & CellSTACK2 tissueculture treated flask at 1.00E+04 cells per cm2 seed density.Perform 100% medium exchange from both flasks on day 3.Harvest Corning T-150 & CellSTACK2 flasks on day 4 post seeding and seedspinner microcarrier culture.

Passage 2:

Expand cells in 2×200 mL spinner flasks at 10 cm2/mL microcarrierdensity using SoloHill's Xeno-free prototype microcarrier.Seed microcarrier cultures at 1.00E+04 cells per cm2 seed density andT-25 as flatware control flask.Perform 80% batch volume medium exchange from spinners and T-25 flaskson day 3.Harvest both microcarrier and T-25 flasks on day 4 post seeding and seedspinner microcarrier culture.

Passage 3:

Expand cells in 3×300 mL spinner flasks at 10 cm2/mL microcarrierdensity using SoloHill's Xeno-free prototype microcarrier.Seed microcarrier cultures at 1.00E+04 cells per cm2 seed density andT-25 as flatware control flask.Perform 80% batch volume medium exchange from spinners and T-25 flaskson day 3.Harvest both microcarrier and T-25 flasks on day 4 post seeding.Seed microcarrier-stir tank bioreactor for exosome production.

Passage 4:

Expand cells into a 2.5 L microcarrier-stir tank at 10 cm2/mL surfacearea to medium ratio.Seed cultures at 1.00E+04 cells per cm2 seed density and T-25 asflatware control flask.Perform 80% batch volume medium exchange on day 2.On day 3 rinse all cultures with 2× cell culture volumes of DPBScontaining Ca and Mg.Add exosome production medium (DMEM-1% Glutamax) to all cultures at 10cm2/mL surface area to medium volume ratio.On day 5 collect harvest spent medium from all cultures, filter using0.45 μm Nalgene rapid flow system and freeze at −20° C.

Procedures: Medium Composition DMEM 1× (Corning ref #10-013-CV) 1%Glutamax (Thermo ref #35050061)

3% Human platelet lysate (Stemulate from Cook Reagentec PG-NH-500)Cell harvest protocol for Planar cultureSettle microcarriers and remove maximum volume of spent medium withoutremoving microcarriers.Wash microcarrier culture with DPBS 2× time at 0.1 mL/cm2 volume tosurface area ratio.Add 37° C. warmed TrypLE 5× enzyme at 0.012 mL/cm2 and incubate flask atroom temperature for ˜15 minutes.Add complete medium at 0.024 mL/cm2 to quench TrypLE 5× activity.Perform viable cell count using NC200 cell count instrument.

Nuclei Count Protocol for Microcarrier Culture

Obtain 4-5 mL of microcarrier culture from bioreactor or spinner flaskSettle microcarriers and remove maximum volume of spent medium withoutremoving microcarriers.Add 1.5 mL Nucleocounter Reagent A to macrocarrier sample tube andvortex at high speed for a minute.Add 1.5 mL Nucleocounter Reagent B to macrocarrier sample tube andvortex at high speed for a minute.Perform nuclei count using NC200 nuclei count instrument.Medium Collection from STR BioreactorStop all controls and settle microcarriers in the bioreactor vessel.Pump out medium through screen bag into collection bottle at 200mL/minute flowrate using peristaltic pump.Inside BSC pour medium into 0.45 μm Nalgene rapid flow filter system andremove free floating cells.Freeze medium bottles in minus 20° C. freezer.Medium Collection from Spinner FlasksInside BSC pour microcarrier culture into 0.45 μm Nalgene rapid flowfilter system and remove free floating cells as well as microcarriers.Freeze medium bottles in minus 20° C. freezer.

Cell culture set points Tem- Dis- Incubator perature Agitation solvedOxygen CO₂ ° C. rpm (DO) % pH setting % T-Flask 37 n/a n/a n/a 5 ± 1CellSTACK 2 37 n/a n/a n/a 5 ± 1 Spinner flask 37 35 n/a n/a 5 ± 1 STRbioreactor 37 35 50 7.35 n/aFIG. 31 shows mPDL1-Fc-GPI production, growth parameters, and analyteconcentrations from a 2.6 L culture in a Stirred Tank Single-Use (STR)bioreactor. Day 2: 80% batch volume medium was exchanged (1′ increase inglucose and decreased in lactate) Day 3: rinse culture with 2× cellculture volumes of DPBS containing Ca and Mg. (2^(nd) increase inglucose and decreased in lactate). Add exosome production medium(DMEM-1% Glutamax) to culture at 10 cm²/mL surface area to medium volumeratio.

mPDL1 was purified using the purification process outlined above (FIGS.32-33).

Example 16 PD-L1-Fc-GPI and PDL2-Fc-GPI Exosomes Increase PD-1 Signaling

The purified exosomes were tested using the modified DiscoverX Assay inFIG. 12A. Approximately a 1000× increase in Relative Light Units (RLU)was achieved for Jurkat signaling cells treated with PD-L1 or PD-L2labeled exosomes when compared to soluble PD-L1-Fc or PD-L2-Fc ligandsalone, respectively. Therefore, it takes 1000× less μg/ml of PD-L1 orPD-L2 on the engineered exosomes to activate PD-1 over solubilizedligands, PD-L1-Fc or PD-L2, achieve the same RLU signaling. FIG. 12Bshow a dose-response curves for the PD-L1 and PD-L2 exosomes vs solublePD-L1 and PD-L2 signaling bioassay. FIG. 12B shows dose-response curvesfor the PD-L1 and PD-L2 exosomes comprising an Fc linker and GPI stickybinder vs. soluble ligands with an Fc domain linker. These results showthat the PD-L1 and PD-L2 polypeptides fused with the Fc and GPI domainson EVs have a more potent effect on PD-1 signaling than the solubleligands alone.

Example 17 In Vivo Assay—Therapeutic Effect of mPD-L1 Exosomes in anExperimental Autoimmune Uveoretinitis (EAU) Model in Lewis Rats

Lewis rats were challenged with retinal antigen interphotoreceptorretinoid-binding protein (IRBP) peptide. This model can be used to studyanterior and posterior chamber dependent EAU. Rats were immunized on Day1 with EAU presenting typically at Day 6. Clinical scores in the ratwere determined. The EAU dosing schedule is shown in FIG. 13A. EAUdosing test article are shown in the following table.

EAU dosing test articles Unmodified mPD-Ll-Fc-GPI mPD-L1-Fc-GPI mPD-L1Exosomes (IVT) Exosomes 1X (IVT) Exosomes 10X (IVT) Exosomes (IV) Dose 2ul 2 ul 2 ul 5 ml/kg Total protein 40 ug/ml 40 ug/ml 400 ug/ml 40 ug/mlconcentration Total protein 80 ng/eye 80 ng/eye 800 ng/eye 50 ug/animaladministered Exosome 5.7 × 10¹⁰/ml 2.34 × 10¹⁰/ml 2.34 × 10¹¹/ml 2.34 ×10¹⁰/ml concentration Total exosomes 4.7 × 10⁷       4.7 × 10⁷     4.7 ×10⁸    2.93 × 10¹⁰    administered *IVT-intravitreal, IV-intravenousThe study design is outlined below:

Group Test Article N Route Concentration Dosage Regimen 1 Cyclosporine 8p.o. 1 mg/mL 10 mg/kg BID from day 0 to Day 20 2 Negative control (PBS 8Intravitreal both 1× 2-3 μL Day 6, Day 12, vehicle) eyes and Day 16 3Unmodified exosomes 8 Intravitreal both 1× (~40 ug/ml) 2-3 μL Day 6 andDay (Control exosomes) eyes 12 4 mPD-L1-Fc-GPI (40 8 Intravitreal both1× (~40 ug/ml) 2-3 μL Day 6, Day 12, ug/ml) eyes and Day 16 5mPD-Ll-Fc-GPI (40 4 Intravenous 1× (~40 ug/ml) 5 mL/kg Day 1, Day 6,ug/ml) Injection Day 12, and Day 16 6 No IRBP peptide but 4 Intravitrealboth 1× (~40 ug/ml) 2-3 μL Day 6, Day 12, treated with Test Agent eyesand Day 16 B (for tolerability) 7 mPD-L1-Fc-GPI (400 8 Intravitreal both1× (400 ug/ml) 2-3 μL Day 6, Day 12, ug/ml) eyes and Day 16Clinical Scores were determined as follows:

EAU Clinical Scores in Rats Score Clinical Criteria 0 No disease; eye istranslucent and reflects light(red reflex) 0.5 Dilated blood vessels inthe iris (trace) 1 Engorged blood vessels in the iris; abnormal pupilcontraction 2 Hazy anterior chamber;decreased red reflex 3 Moderatelyopaque anterior chamber,but pupil still visible; dull red reflex 4Opaque anterior chamber and obscured pupil; red reflex absent; proptosisEach higher grade includes the criteria of the preceding one.

It was discovered that there is a statistically significant initialreduction in EAU in mPDL1 exosome treated rats via either theintravitreal and intravenous delivery modes as compared with untreatedanimals (FIG. 13A). Rat weight did not change post immunization (FIG.13C).

Example 18 Purification of Exosomes Labeled with Type II MembraneProteins

The inventors designed, engineered, and purified pcDNA5-FRT-4F2-4-1BBLexosomes by the methods provided herein (FIG. 34). Several embodimentsof the 4-1BBL labeled exosomes are shown in FIG. 35. Cell expression ofthe 4F2-4-1BBL was confirmed (data not shown). FIGS. 92A-92B shows thepurification of 4F2-4-1BBL exosomes.

Example 19 Purification of Luminal Labeled Exosomes (Internal Loading)

In addition to Type I and Type II display fusion proteins on the surfaceof an EV, exosomes can be loaded with fusion proteins that are localizedto the lumen of the phospholipid bilayer of the exosome (FIG. 37). TheMyr/Palm sequence used herein when fused to mScarlet the fusion proteininto the luminal interior of extracellular vesicles. Fluorescence at anexcitation wavelength 470 nm and emission wavelength of 665-720 nm peaksin SEC fractions 7, 8, and 9. SEC fractions 7, 8, and 9 contain exosomesas demonstrated by the dot blot. Fraction 8 was further analyzed forexosome quantification using an ExoView system (FIG. 38). Unmodifiedexosomes do not show fluorescence. Exosomes show near 80% loading withMyr/Palm-mScarlet. The remaining 20% were out of the detection limit.Thus, nearly 100% internal loading was achieved using the specificMyr/Palm sequence.

NanoLuc luciferase expressing exosomes were also purified with theMyr/Palm sequence incorporated into the vector encoding the fusionpolypeptide. A Qubit fluorometer was used to measure total protein andPromega Nano-Glo substrate and plate luminometer to measure luminescence(FIG. 39A). Tetraspanin characterization of exosomes was performed anddetermined that the NanoLuc luciferase exosomes were internally loadedand purified in fraction 8 (FIG. 39B).

What is claimed is:
 1. An engineered extracellular vesicle comprising: at least one fusion polypeptide comprising: (i) at least one protein of interest (POI) domain or a fragment thereof; and (ii) at least one vesicle targeting domain, wherein the POI domain is in an extracellular position relative to a lipid membrane of the extracellular vesicle.
 2. The engineered extracellular vesicle of claim 1, wherein the extracellular vesicle is an exosome.
 3. The engineered extracellular vesicle of claim 1 or claim 2, wherein the protein of interest (POI) domain or a fragment thereof is a N-terminal domain of the fusion polypeptide.
 4. The engineered extracellular vesicle of any one of claims 1-3, wherein the vesicle targeting domain is a C-terminal domain of the fusion polypeptide.
 5. The engineered extracellular vesicle of any one of claims 1-4, wherein the fusion polypeptide comprises at least two POI domains and/or at least two exosome targeting domains.
 6. The engineered extracellular vesicle of any one of claims 1-5, wherein the fusion polypeptide further comprises a peptide linker.
 7. The engineered extracellular vesicle of any one of claims 1-6, wherein the fusion polypeptide further comprises a fragment crystallizable region (Fc) domain.
 8. The engineered extracellular vesicle of any one of claims 1-7, wherein the vesicle targeting domain is in a luminal position relative to the lipid membrane of the extracellular vesicle.
 9. The engineered extracellular vesicle of any one of claims 1-7, wherein the vesicle targeting domain in an exterior position relative to the lipid membrane of the extracellular vesicle.
 10. The engineered extracellular vesicle of any one of claims 1-9, wherein the POI domain is selected from the group consisting of: Table
 1. 11. The engineered extracellular vesicle of any one of claims 1-10, wherein the POI domain is PD-L1 or a fragment thereof.
 12. The engineered extracellular vesicle of any one of claims 1-11, wherein the POI domain is PD-L2 or a fragment thereof.
 13. The engineered extracellular vesicle of any one of claims 1-12, wherein the POI domain is FGL1 or a fragment thereof.
 14. The engineered extracellular vesicle of any one of claims 1-13, wherein the POI domain is 4-1BBL or a fragment thereof.
 15. The engineered extracellular vesicle of any one of claims 1-14, wherein the POI domain is CTLA-4 or a fragment thereof.
 16. The engineered extracellular vesicle of any one of claims 1-15, wherein the POI domain substantially binds to one or more of a target polypeptide.
 17. The engineered extracellular vesicle of claim 16, wherein the target polypeptide is selected from the group consisting of: Table
 2. 18. The engineered extracellular vesicle of any one of claims 1-17, wherein the vesicle targeting domain is selected from the group consisting of: Table
 3. 19. The engineered extracellular vesicle of any one of claims 1-18, wherein the linker is in an exterior position relative to the lipid membrane of the extracellular vesicle.
 20. The engineered extracellular vesicle of any one of claims 1-18, wherein the linker is a transmembrane linker.
 21. The engineered extracellular vesicle of any one of claims 1-18, wherein the linker is in a luminal position relative to the lipid membrane of the extracellular vesicle.
 22. The engineered extracellular vesicle of any one of claims 1-21, wherein the extracellular vesicle does not comprise an endogenous POI polypeptide.
 23. A composition comprising a plurality of the engineered extracellular vesicles of any one of claims 1-22.
 24. The composition of claim 23, further comprising a pharmaceutically acceptable carrier.
 25. An engineered extracellular vesicle comprising: (a) a first fusion polypeptide comprising: (i) at least one protein of interest (POI) domain or a fragment thereof, and (ii) at least one vesicle targeting domain, wherein the at least one POI domain is in an extracellular position relative to a lipid membrane of the extracellular vesicle, (b) a second fusion polypeptide comprising: (i) at least one protein of interest (POI) domain or a fragment thereof; and (ii) at least one vesicle targeting domain, wherein the POI domain is in an extracellular position relative to a lipid membrane of the extracellular vesicle, and wherein the at least one vesicle targeting domain is within a lipid membrane of the extracellular vesicle.
 26. A composition comprising two or more of the engineered extracellular vesicles selected from any one of claims 1-25.
 27. An extracellular vesicle composition comprising: a plurality of artificial synapses, wherein each artificial synapse comprises (i) an extracellular vesicle; (ii) one or more sticky binders; and (iii) one or more signaling domains.
 28. The composition of claim 27, wherein the extracellular vesicle comprises an exosome.
 29. The composition of claim 27, wherein the one or more sticky binders is selected from the group consisting of: a GPI anchor, a fatty acetylation site, and a prenylation site.
 30. The composition of claim 27, wherein the signaling domain comprises one or more of: PD-L1, PD-L2, CTLA-4 (CD152), 4-1BBL (CD137L), HVEM (CD270), FGL1, OX-2 (CD200), Galectin-9, PVR (CD155), Nectin-2 (CD112) isoform alpha, Nectin-2 (CD112) isoform beta, Nectin-2 (CD112) isoform delta, IL-10, TSG-6, B7-H3 (CD276), B7-H4 (VTCN1), B7-H5 (VISTA), B7-H7 (HHLA2), BTNL1, VSIG8, VSIG3 (IGSF11), VSIG4, TIM-3 (HAVCR2), TIM-4 (TIMD4), CEACAM1, BTN3A1, BTN3A2, BTN2A1, BTNL8, BTN2A2, BTN1A1, TIGIT, CD27L (CD70), CD30L (CD153), GITRL, CD40L (CD154), LIGHT (CD258), TL1, CD80, CD86, LFA-3 (CD58), SLAM (CD150), CD40, CD28, CD28H, CD2, LFA-3 (CD58), CD48, CD226, DR3, DcR3, FasL, TIM-1 (CD365), PD-1, or active fragment thereof.
 31. A method of producing the engineered extracellular vesicle or the composition of any one of claims 1-30, comprising: (a) providing a population of cells expressing a vector construct encoding one or more sticky binder and one or more signaling domains; and (b) isolating a plurality of artificial synapses from the population of cells.
 32. A method of producing the engineered extracellular vesicle or the composition of any one of claims 1-30, comprising: (a) providing a population of cells expressing a vector construct encoding one or more sticky binder and one or more signaling domains; and (b) isolating a plurality of artificial synapses from the population of cells; and (c) purifying the plurality of artificial synapses from the population of cells.
 33. The method of claim 31 or claim 32, the isolating is via size exclusion chromatography.
 34. The method of claim 32, wherein the purifying is via multimodal chromatography.
 35. The method of any of claims 31-34, further comprising performing an assay for POI binding to a target polypeptide.
 36. The method of claim 35, wherein the vector construct further encodes a promoter.
 37. The method of claim 36, wherein the promoter is a tissue-specific promoter or an inducible promotor.
 38. A method of modulating inflammation in a subject, the method comprising: administering a composition comprising a plurality of engineered extracellular vesicles to a subject in need thereof, wherein the engineered extracellular vesicles comprise at least one fusion polypeptide comprising: (i) at least one protein of interest (POI) domain or a fragment thereof; and (ii) at least one vesicle targeting domain.
 39. The method of claim 38, wherein the extracellular vesicle comprises an exosome.
 40. The method of any one of claims 38-39, further comprising selecting a subject that has or is suspected of having an autoimmune disease or an inflammatory disease or condition.
 41. The method of any one of claims 38-40, wherein the vesicle targeting domain is selected from the group consisting of: a Glycosylphosphatidylinositol (GPI) anchor, a fatty acetylation site, and a prenylation site.
 42. The method of any one of claims 38-41, wherein the vesicle targeting domain is a GPI anchor.
 43. The method of any one of claims 38-41, wherein the vesicle targeting domain is C1C2.
 44. The method of any one of claims 38-43, wherein the protein of interest (POI) domain comprises one or more of: PD-L1, PD-L2, CTLA-4 (CD152), 4-1BBL (CD137L), HVEM (CD270), FGL1, OX-2 (CD200), Galectin-9, PVR (CD155), Nectin-2 (CD112) isoform alpha, Nectin-2 (CD112) isoform beta, Nectin-2 (CD112) isoform delta, IL-10, TSG-6, B7-H3 (CD276), B7-H4 (VTCN1), B7-H5 (VISTA), B7-H7 (HHLA2), BTNL1, VSIG8, VSIG3 (IGSF11), VSIG4, TIM-3 (HAVCR2), TIM-4 (TIMD4), CEACAM1, BTN3A1, BTN3A2, BTN2A1, BTNL8, BTN2A2, BTN1A1, TIGIT, CD27L (CD70), CD30L (CD153), GITRL, CD40L (CD154), LIGHT (CD258), TL1, CD80, CD86, LFA-3 (CD58), SLAM (CD150), CD40, CD28, CD28H, CD2, LFA-3 (CD58), CD48, CD226, DR3, DcR3, FasL, TIM-1 (CD365), PD-1, or active fragment thereof.
 45. The method of any one of claims 38-44, wherein the protein of interest (POI) domain is PD-L1 or a fragment thereof.
 46. The method of any one of claims 38-44, wherein the protein of interest (POI) domain is PD-L2 or a fragment thereof.
 47. The method of any one of claims 38-44, wherein the protein of interest (POI) domain is CTLA-4 or a fragment thereof.
 48. The method of any one of claims 38-44, wherein the protein of interest (POI) domain is HVEM or a fragment thereof.
 49. The method of claim 40, wherein the inflammatory disease and/or condition is acute.
 50. The method of claim 40, wherein the inflammatory related disease and/or condition is chronic.
 51. The method of claim 38, wherein administering the composition comprises injection, topical administration, or inhalation.
 52. Use of a composition comprising a plurality of engineered extracellular vesicles, the engineered extracellular vesicles each comprising: at least one fusion polypeptide comprising: (i) at least one protein of interest (POI) domain or a fragment thereof; and (ii) at least one vesicle targeting domain for the treatment of an inflammatory disease or condition.
 53. Use of a composition comprising a plurality of engineered extracellular vesicles, the engineered extracellular vesicles each comprising: at least one fusion polypeptide comprising: (i) at least one protein of interest (POI) domain or a fragment thereof, and (ii) at least one vesicle targeting domain for the treatment of an autoimmune disease or condition.
 54. Use of a composition comprising a plurality of engineered extracellular vesicles, the engineered extracellular vesicles each comprising: at least one fusion polypeptide comprising: (i) at least one protein of interest (POI) domain or a fragment thereof; and (ii) at least one vesicle targeting domain for the treatment of cancer. 